General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.

Users may download and print one copy of any publication from the public portal for the purpose of private study or research.

You may not further distribute the material or use it for any profit-making activity or commercial gain

You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Downloaded from orbit.dtu.dk on: Jan 14, 2022

Bioremediation of lignin derivatives and phenolics in wastewater with lignin modifyingenzymes: Status, opportunities and challenges

Singh, Anil Kumar; Bilal, Muhammad; Iqbal, Hafiz M.N.; Meyer, Anne S.; Raj, Abhay

Published in:Science of the Total Environment

Link to article, DOI:10.1016/j.scitotenv.2021.145988

Publication date:2021

Document VersionPublisher's PDF, also known as Version of record

Link back to DTU Orbit

Citation (APA):Singh, A. K., Bilal, M., Iqbal, H. M. N., Meyer, A. S., & Raj, A. (2021). Bioremediation of lignin derivatives andphenolics in wastewater with lignin modifying enzymes: Status, opportunities and challenges. Science of theTotal Environment, 777, [145988]. https://doi.org/10.1016/j.scitotenv.2021.145988

Science of the Total Environment 777 (2021) 145988

Contents lists available at ScienceDirect

Science of the Total Environment

j ourna l homepage: www.e lsev ie r .com/ locate /sc i totenv

Review

Bioremediation of lignin derivatives and phenolics in wastewater withlignin modifying enzymes: Status, opportunities and challenges

Anil Kumar Singh a,b, Muhammad Bilal c,⁎, Hafiz M.N. Iqbal d, Anne S. Meyer e,⁎, Abhay Raj a,b,⁎a Environmental Microbiology Laboratory, Environmental Toxicology Group CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow226001, Uttar Pradesh, Indiab Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, Indiac School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, Chinad Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey 64849, Mexicoe Department for Biotechnology and Biomedicine, Technical University of Denmark, Building 221, DK-2800 Lyngby, Denmark

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Systematic outline of key pollutant-generating steps in the paper and pulpindustry

• Toxic pollutants chemistry and their en-vironmental and human health impact

• Novel bioremediation approaches forpollutant mitigation in wastewater

• Oxidative catalytic potential of ligninmodifying enzymes in wastewatertreatment

• Summary of forward-looking biotech-nology tools to advance biobasedremediation

⁎ Corresponding authors.E-mail addresses: bilaluaf@hyit.edu.cn (M. Bilal), asme

https://doi.org/10.1016/j.scitotenv.2021.1459880048-9697/© 2021 Published by Elsevier B.V.

a b s t r a c t

a r t i c l e i n f o

Article history:Received 2 January 2021Received in revised form 14 February 2021Accepted 15 February 2021Available online 20 February 2021

Editor: Frederic Coulon

Keywords:Environmental pollutantsCatalytic eliminationLignin-modifying enzymesLigninIndustrial processesToxicity

Lignin modifying enzymes from fungi and bacteria are potential biocatalysts for sustainable mitigation of differ-ent potentially toxic pollutants in wastewater. Notably, the paper and pulp industry generates enormousamounts ofwastewater containinghigh amounts of complex lignin-derived chlorinatedphenolics and sulfonatedpollutants. The presence of these compounds inwastewater is a critical issue from environmental and toxicolog-ical perspectives. Some chloro-phenols are harmful to the environment and human health, as they exert carcino-genic,mutagenic, cytotoxic, and endocrine-disrupting effects. In order to address thesemost urgent concerns, theuse of oxidative ligninmodifying enzymes for bioremediation has come into focus. These enzymes catalyzemod-ification of phenolic and non-phenolic lignin-derived substances, and include laccase and a range of peroxidases,specifically lignin peroxidase (LiP), manganese peroxidase (MnP), versatile peroxidase (VP), and dye-decolorizing peroxidase (DyP). In this review, we explore the key pollutant-generating steps in paper and pulpprocessing, summarize themost recently reported toxicological effects of industrial lignin-derived phenolic com-pounds, especially chlorinated phenolic pollutants, and outline bioremediation approaches for pollutant mitiga-tion inwastewater from this industry, emphasizing the oxidative catalytic potential of oxidative ligninmodifyingenzymes in this regard. We highlight other emerging biotechnical approaches, including phytobioremediation,bioaugmentation, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based technology, pro-tein engineering, and degradation pathways prediction, that are currently gathering momentum for the mitiga-tion ofwastewater pollutants. Finally, we address current research needs and options formaximizing sustainablebiobased and biocatalytic degradation of toxic industrial wastewater pollutants.

© 2021 Published by Elsevier B.V.

@dtu.dk (A.S. Meyer), araj@iitr.res.in (A. Raj).

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22. Structural and chemical aspects of lignin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33. Lignin processing and pulp bleaching treatments-based wastewater pollutants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

3.1. Technical lignin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53.2. Health hazards associated with wastewater from the paper industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

4. The effluents of the paper industry: environmental impact and implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65. Current concerns and need for bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

5.1. Conventional bioremediation approaches for pollutants mitigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75.1.1. Biostimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85.1.2. Bioaugmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85.1.3. Microbial bioreactors in bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85.1.4. Phytoremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

5.2. The core advantages of bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105.3. The key disadvantages of bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

6. Lignin-modifying enzymes for sustainable mitigation of lignin, phenolics, and a wide variety of pollutants . . . . . . . . . . . . . . . . . . . . 116.1. Plant based peroxidases for pollutants remediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116.2. Microbial biodegradation of lignin and its derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116.3. Biocatalytic biodegradation of phenolic compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126.4. Biodegradation of endocrine-disrupting chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126.5. Biodegradation of chlorinated phenolics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

7. Recent advances in bioremediation for pollutant remediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137.1. In silico approaches, molecular modeling, and degradation pathway prediction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137.2. Protein engineering approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147.3. Genetically engineered microbes (GMOs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147.4. Gene editing CRISPR aided approaches in bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

8. Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159. Concluding remarks and research trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Declaration of competing interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

1. Introduction

Environmental pollutants derived from large scale industrialwood processing represent a critical global challenge for sustainabledevelopment. The discharge of processing pollutants from the paperand pulp industry has improved significantly during the last10–20 years, but this industry still generates wastewater at an im-mense scale that contains high amounts of phenolic, chlorinated,complex lignin-derived and sulfonated pollutants (Mandeep et al.,2019; Singh and Raj, 2020). In China, for example, the demand forpaper products and hence paper and pulp effluent loads increasedenormously during the decades of booming economic growth andthese effluents now contribute about 10% of China's industrial waste-water emissions, but 25% of the chemical oxygen demand (COD), andthe paper industry is thus considered a major source of industrialwastewater emissions in China (Zhang et al., 2020). Likewise, inIndia, the paper and pulp industry, which supplies about 3% of theworld's paper production, is classified as one of the most water-polluting industries (National Mission for Clean Ganga, 2019). Theindustry encompasses wood-based paper processing mills andsmaller-scale industrial pulp manufacturing from agro-industriallignocellulosic residues (Kumar et al., 2020a, b, c).

The high amounts of wastewater and the discharge of significantamounts of potentially harmful compounds are produced during sev-eral different papermaking process stages, including pulping, bleaching,andwashing (Chandra et al., 2018; Mehmood et al., 2019). Per each tonof paper products produced, it is estimated that 70–225m3 ofwastewa-ter effluent is discharged; approximately 20–25 m3 is from the pulpingstep, and up to 80–100 m3 stems from the bleaching process— the vol-umes vary depending on the raw material, processing regime, and ex-tent of water recirculation (Hubbe et al., 2016; Wagle et al., 2020). Toput these numbers in perspective, a conservative estimate is thatabout 2.5 million tons of chemical pulp is produced per year in India,

2

of which 60% is bleached using chlorine and chlorine-based chemicals(Malhotra et al., 2013).

The paper and pulp industry strives to transition to become moresustainable, and elemental chlorine-free and total chlorine-free paperprocesses do exist, which have reduced the presence of toxic substancesprofoundly in certain countries (Hubbe et al., 2016). Yet, both conven-tional chemical pulping and classical bleaching steps based on sequen-tial addition of chlorine, hypochlorite, and chlorine dioxide, along withthe use of acid sulfur dioxide washing and sodium dithionite addition,are still widely used to obtain bright, white paper products (Kumaret al., 2020a, b, c; Malhotra et al., 2013). These processing steps resultin the discharge of numerous free constituent chlorophenols and re-lated compounds, some of which resist spontaneous degradation. Thewastewater produced from major current paper and pulp processingsteps is thus characterized by containing an array of problematic sub-stances, i.e. chlorophenols, sulfonated fragments of lignin, a range of sul-fide byproducts, various resins, along with different high biologicaloxygen demand products, and high levels of inorganic salts(Choudhary et al., 2015; Kumar et al., 2020a, b, c). The effluents are po-tentially toxic and hazardous to the environment (Fig. 1). In addition, asdiscussed later, the toxicity effects of some of these compounds onhuman health are significant and include mutagenic and possibleendocrine-disrupting effects (Chandra et al., 2018).

As hinted above, the pulping and bleaching are the main stepswherein different toxic contaminants are formed, i.e. the chlorophenols,the lignin-derived phenolic compounds, the sulfonated substances, andthe volatile organochlorine compounds (Du et al., 2014; Qin et al., 2019;Singh et al., 2019). The effluents from the pulping and bleachingprocesses are indeed characterized by their high COD (1000 to7000 mg L−1) and their low biodegradability, with biodegradability/COD ratios ranging from 0.02 to 0.07 even at moderate levels ofsuspended solids (500 to 2000 mg L−1) (Hubbe et al., 2016; Mehmoodet al., 2019; Mounteer et al., 2007; Uğurlu and Karaoğlu, 2009).

Fig. 1. Schematic representation of a typical paper making process with emission of different pollutants from the paper industry. A: Raw material: Cellulose feedstock from plants. B:Different chemical process during paper manufacturing: Major processes Kraft pulping and bleaching. Black liquor is the major fluid, and it contains diverse chlorinated, phenolic, andcomplex pollutants, including potential EDCs. Lignin-modifying enzymes may help eliminate the pollutants in an eco-friendly manner.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

The reduction of environmental pollutants from the paper indus-try is thus a critical Global issue in achieving a sustainable environ-ment (Deeba et al., 2018; National Mission for Clean Ganga, 2019).To address this concern, new bio-catalysis-mediated remediationstrategies involving enzymes are currently being explored as envi-ronmentally friendly approaches to remove toxic wastewater pollut-ants (Ashrafi et al., 2015; Baghel et al., 2020; Kalyani et al., 2016;Zdarta et al., 2019). The enzymes at the center stage of this new di-rection include various lignin modifying enzymes, namely laccaseand various peroxidases, as follows: laccases (EC 1.10.3.2), whichare produced by fungi, bacteria, and even in plants, catalyze the oxi-dation of phenols, including phenoxyl groups in lignin and lignin-derived compounds during the reduction of O2 (Sitarz et al., 2016;Singh et al., 2021b). Lignin modifying peroxidases catalyze the con-version of a wide variety of lignin-derivatives and phenolics usinghydrogen peroxide (H2O2) as co-substrate for the oxidation reaction(Elisashvili et al., 2018; Riyadi et al., 2020; Sitarz et al., 2016). Theseperoxidases include LiP (EC 1.11.1.14), MnP (EC 1.11.1.13), VP (EC1.11.1.16), and DyP (EC 1.11.1.19), are produced by various lignin-degrading fungi and bacteria, and can even be found in certainplant materials (Akhtar and Husain, 2006; Ali et al., 2021; Chauhan,2020; Singh et al., 2013; Vaidya et al., 2019). Laccases can directlycatalyze the oxidation of phenolic lignin compounds (Munk et al.,2015), and a fungal laccase was moreover recently shown able toeven degrade non-phenolic pharmaceuticals such as naproxen(containing a 2-methoxy-naphtalene core) and diclofenac (contain-ing a di-chloro-benzene moiety) (Zdarta et al., 2019). Laccases andthe lignin modifying peroxidases have been reported to catalyzethe oxidation of lignin model compounds and to have potential ascatalysts for bioremediation of phenolic, including oligophenolicand chlorophenolic compounds, and even non-phenolic compounds,some of which are considered as environmental contaminantsand endocrine-disrupting compounds (EDCs) (Falade et al., 2018;Grelska and Noszczyńska, 2020; Kalyani et al., 2016; Kamimuraet al., 2019; Paz et al., 2020; Verma et al., 2020).

3

Toour knowledge, a clear overviewoutlining the effects, advantages,disadvantages, and application records of these enzymes in relation toscavenging of industrial pollutants, including chlorinated phenols inwastewater does not exist. This critical review attempts to outline thesignificant polluting steps in paper manufacture. It particularly focuseson addressing newer biotechnological options for sustainable, efficient,and eco-friendlymitigation of themost hazardous phenolic and chloro-phenolic wastewater compounds. The core of the review focuses onexploiting oxidative microbial lignin modifying enzymes, includinglaccases and certain peroxidases for conversion and removal of industri-ally relevant toxic effluent compounds, especially the toxic pollutantsresulting from industrial pulping and pulp bleaching in pulp papermanufacturing processes. Moreover, other bioremediation techniquesand the use of predictive and advanced molecular tools, includingnovelmolecular andmicrobial engineering approaches and in silico pre-diction approaches are considered for enhanced bioremediation.

2. Structural and chemical aspects of lignin

Lignin consists of three specific phenylpropanyl units thatare biopolymerized in the plant cell wall to function as athree-dimensional amorphous polymer: guaiacyl alcohol (G unit),p-coumaryl alcohol (Hunit), syringyl alcohol (S unit). In the lignin poly-mer, the three constructive monolignols are attached and linked by oneof the two or both types of linkage forming a C\\C bond or a C\\O\\Cbond. In more detail, the units are mainly linked by aryl ether (β-O-4),phenylcoumaran (β-5), resinol (β–β), biphenyl ether (5-O-4),dibenzodioxocin (5–5/β-O-4) type linkages (Munk et al., 2015). As astructural material of wood, lignin is vital and might comprise up to25% of dry plant biomass. Lignin and its synthesis vary slightly fromplant to plant, and differences occur between chemical components, es-pecially in linkages among different plant types, either softwood orhardwood (Mu et al., 2018; Sher et al., 2020). Typically, more thantwo-thirds of monolignols units are connected by ether linkages(Guadix-Montero and Sankar, 2018; Ralph et al., 2004). Fig. 2 displays

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

the components of the lignin polymer including lignin monomer units,coupled dimeric moieties as well as dibenzodioxocin and different link-ages alongside percentages.

Due to it being a polyaromatic, ether-linked hydrophobic polymer,lignin is “waterproof” and quite resistant to biological degradation. Forthis reason, harsh chemicals and high temperatures are used in paperand pulp processing, in turn resulting in the generation of harmfulpaper mill effluents (Kamimura et al., 2019; Pu et al., 2015). Theprime purpose of the pulping process is to remove the lignin withoutdamaging the cellulose fiber strength. Hence, a critical point in paperproduction is the removal of the lignin from the cellulose fibers andthe elimination or bleaching of any impurities that cause discolorationand possible disintegration of the paper (Bajpai, 2018). As outlinedbelow, the pulping process relies on chemical additives, followed bybleaching that involves a series of chemical and oxidative treatmentsteps to obtain white paper (Bajpai, 2018).

3. Lignin processing and pulp bleaching treatments-based wastewa-ter pollutants

Different types of lignin-related compounds have been identifiedeven in treated wastewater from paper industries (Chung andWashburn, 2016). To produce high-quality paper, lignin and hemicellu-lose contents must be removed. For this purpose, the pulp undergoestreatment with alkali, and sodium sulfide, chlorine dioxide, or sulfiteor bisulfite at elevated temperature, i.e. beyond 150 °C (usually at170–180 °C). This chemical digestion treatment breaks the bonds thattie the lignin to hemicellulose and cellulose and even hydrolyzes the lig-nin and turns the lignin into water-soluble substances (Mathew et al.,2018; Shrotri et al., 2017). The combined alkali and sulfide pulping arecalled the Kraft process or sulfate pulping process. The process wasinvented about 140 years ago in Germany in 1879, yet, although Kraftpulping has been improved since then, the principles behind thispulping procedure remains the commercially dominant pulp processfor converting wood to a pulp for papermaking today. As discussed

Fig. 2.Graphical representation of lignin and its different aspects. A: 2D depiction of three primain a different types of lignin based on plant origin. C: Lignin polymer including respective perc

4

further below, Kraft lignin, soda lignin, organosolv lignin, andsulfonated lignin are the most common types of technical ligninresulting from the pulping process. The pulping process may also in-clude the reaction of residual lignin with chlorine dioxide, a processingstep that results in the formation of a significant amount of adsorbableorganic halogen (Shi et al., 2019). Also, the addition of different organicsolvents, i.e., alcohols, acids, esters, and ketones may be used duringpulping to promote the cleavage of lignin bonds between monomerunits (Shrotri et al., 2017). As a result, free lignin units form duringthe depolymerization of lignin.

After digestion, the rawpulp is screened and is usually cleaned againto remove the water. A noticeable amount (up to 6%) of lignin contentsis left and persists in the raw cellulose, which, therefore, cannot be useddirectly as paper (Julkapli and Bagheri, 2016). For further breakdownand modification of lignin contents, the pulp then undergoes ableaching process (Fortunati et al., 2016; Hubbe et al., 2016; Kumaret al., 2020a, b, c). Pulp bleaching is usually accomplished using a seriesof chemical treatments designed to produce white, high-quality paperproducts. The most common bleaching agents include H2O2, sodiumsulfite, sodium hydroxide, chlorine, chlorine dioxide, and also enzymes,notably endo-xylanases, which have been reported useful in thebleaching process of woody pulp (Bajpai, 2018; Kumar et al., 2020a, b,c). In this series of mechanical pulp bleaching processes, that are de-signed to remove chromogens and brighten the pulp with minimumloss of mass, H2O2 is currently the most widely used chemical (Bajpai,2018). Chelating agents may be added to control metal ions that other-wise may impart the bleaching via decomposing the H2O2 (Hintz,2001).

The initiation of the bleaching process starts with oxygen and ozone,followed by the treatment with bleaching agents. Treated or bleachedpulp is washed with sodium hydroxide, then treated with chemicalsin a sequence. During these treatments lignin becomes modified, andas a result, sulfonated lignin or lignosulfonates are generated in signifi-cant amounts as byproducts (Hintz, 2001). Due to the profound numberof lignin functional groups as well as the large number of carbohydrate

ry lignin polymer-forming unit (monomer; G; H; S units). B: Percentage ofmonomer unitsentage and constructive linkages.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

degradation products, including oligophenols that can form during heattreatment by self-condensation and other reactions (Rasmussen et al.,2017), many different chemical compound products may be generatedduring industrial pulp and paper processes.

3.1. Technical lignin

The composition of technical lignin varies considerably with the rawmaterial, pulp conditions, and processing chemicals used. The Kraft lig-nin process remains the most dominant industrial chemical pulpingprocedure, which is why Kraft lignin (extracted from pulp mill black li-quor) is the most common type of technical lignin product from thepaper and pulp industry (Zakzeski et al., 2010), yet obviously, the com-position of Kraft lignin varies depending on the rawmaterials and pro-cessing conditions (Ház et al., 2019).

Lignin derivatives from the Kraft process constitute toxic and recal-citrant substances that accounts for the high BOD and COD and causethe dark brown appearance of effluents generated during the pulpingprocess in the paper mill (Roppola et al., 2009). During bleaching ofpulp in the papermaking process, chlorine is reacted with lignin andlignin-derived compounds, chlorinated compounds formedby chemicalalteration, which are present in the pulp (Sudarshan et al., 2017). Inparticular, oxidation, hydrolysis, and pyrolysis (methoxy-substitutedphenols and cresols) generate lignin-derived compounds in high yield(Alekhina et al., 2015). The recalcitrant and toxic compoundsgenerated from pulping and bleaching operations include chlorinatedlignosulfonic acid, chlorinated resin acids, chlorinated phenols, vanil-lins, catechols, benzaldehyde, guaiacols, and syringe-vanillins alongwith chloropropioguaiacols (Choudhary et al., 2015; Thakur, 2004).Somewell-known lignin-derived, phenolic, and complex pollutants, in-cludingEDCs generated from industrial pulp and paper processing oper-ations and their presence in wastewater are listed in Table 1.

For the sake of completion, it should be noted that other commer-cially available lignin forms are soda lignin, hydrolyzed lignin,organosolv lignin, and lignosulfonates (Zhong and Nie, 2017). Lignin-derived value-added products for lignin valorization via biorefineryprocesses are increasingly being investigated for the production of dif-ferent bio-based chemicals (Becker and Wittmann, 2019; Gillet et al.,2017). Lignin usage is sometimes considered in a lignin first conceptin bioeconomy research. The extraction of lignin as a primary product

Table 1Major environmental contaminants emitted from industrial processes, incl. pollutants from panant compounds, their chemical properties and known toxicity or adverse effects.

Compound Molecularformula

Molecularweight

PubChemCID

4-Chloro-2-methoxyphenol C7H7ClO2 158 280505-Chlorovanillin C8H7ClO3 186 29622

2,3,7,8-Tetrachlorodibenzo-p-dioxin C12H4Cl4O2 322 15625

4,5-Dichloroguaiacol C7H6Cl2O2 193 171604-Chlorocatechol C6H5ClO2 144 164962,3′,4,4′,5-Pentachlorobiphenyl C12H5Cl5 326 35823Polychlorinated naphtha-lenes(2,3,6,7-tetra-chloronaphthalene)

C10H4Cl4 265 108070

Dehydroabietic acid C20H28O2 300 943914-Chloro-3-methylphenol C7H7ClO or

C6H3OHCH3Cl143 1732

2-Chlorophenol C6H5ClO 128 72452,4,6-Trichlorophenol C6H3Cl3O 197 6914Pentachlorophenol C6Cl5OH 266 9922-Methoxy phenol C7H8O2 124 4604,5-Dichlorocatechol C6H4Cl2O2 179 18909

6-Chlorovanillin C8H7ClO3 187 29622

3,4-Dichlorophenol C6H4Cl2O 163 7258Chloromethane CH3Cl 50 6327

5

from lignocellulosic materials processing is predicted to expand in thefuture (Radotić and Micic, 2016).

3.2. Health hazards associated with wastewater from the paper industry

As already indicated above, in the paper finishing steps, additivesand chlorine for bleaching are added to achieve the desired paper qual-ity, resulting in the generation of various toxic polychlorinated com-pounds (Table 1). Fortunately, regulatory restrictions enforced sincethe 1990s to control the use of dioxin, polychlorinated phenols, and di-benzofuran in paper manufacturing in North America/Canada andEurope, have limited the levels of dioxins in pulp and paper mill efflu-ents in these countries (Hubbe et al., 2016). However, in other places,it is mentioned that dioxins and furans release into the wastewatermay result from malpractices such as when plastics are used as boilerfuel (National Mission for Clean Ganga, 2019). Dioxins and dioxin-likepolychlorinated biphenyls are notoriously recognized as hazardouschemicals and known to elicit developmental toxicity, carcinogenicity,and endocrine-disrupting properties in humans (Sappington et al.,2015; Urbaniak et al., 2017). The organochlorine compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin has for instance long been known as amultisite carcinogen associated with specific tumors (Torén et al.,1996), and polychlorobiphenyls have been classified as probable carcin-ogens in occupational workers related to pulp and paper industries(Monge-Corella et al., 2008; Soskolne and Sieswerd, 2010; Torén et al.,1996).

Pollutant-rich effluents are generally discharged into water bodiesdirectly or indirectly and thus pose a risk of inducing environmentaltoxicity (Singh et al., 2019). The presence of various carcinogenic andandrogenic components and chloro-lignin in the effluent can triggerthe toxicological impact on human health (Monge-Corella et al.,2008). Also, poly-aromatic hydrocarbons can negatively impacthuman health. These pollutants have often been reported to exert neg-ative effects on the reproductive system of both males and females;moreover, adverse effects on infant development have been detected(Jan et al., 2007; Jan and Vrbic, 2000; Joffe, 2003; Vecoli et al., 2016).

Organosulfur compounds (methyl mercaptan), a specific chemicalalso generated from the pulp and paper industries during chemical pro-cessing, can be released in the water bodies through the generatedwastewater; as a result, damaging of the electron transport system in

per and pulp processes (reported in effluents). The Table includes the individual contami-

Reported/known toxicity References

Target organ toxicity, skin corrosion/irritation (Rajput et al., 2020)Skin irritation, respiratory irritant, target organtoxicity

(Kaur et al., 2019)

Acute toxic, mutagenic environmentallyhazardous

(Malhotra et al., 2013;Thacker et al., 2007)

Aquatic toxicity (Garba et al., 2019)Aquatic toxicity (Lobo et al., 2018)Carcinogenic, POPs, EDCs (Huang et al., 2019)Genotoxicity, mutagenicity, developmentaltoxicity, EDCs, POPs

(Ohura, 2007)

Acute oral toxicity (Hubbe et al., 2016)Aquatic toxicity, mutagenic, skin irritant (Gadupudi et al., 2019)

Aquatic toxicity, genotoxicity, mutagenicity (Foszpańczyk et al., 2018)Genotoxicity, mutagenicity, aquatic toxicity, POPs (Khorsandi et al., 2018)Genotoxicity, mutagenicity, Aquatic toxicity, POPs (Cheng et al., 2015)Acute toxicity, skin irritant (Taylor, 2019)Acute toxicity, target organ toxicity, skin irritant,environmental hazard

(Malhotra et al., 2013)

Target organ toxicity, skin irritant, environmentalhazard

(Malhotra et al., 2013)

Acute toxicity, skin and eye irritation (Choudhary et al., 2015)Carcinogenicity, organ toxicity, cytotoxicity (Arts et al., 2019)

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

living organisms by the mechanism of oxidase inhibition may result(Adeel et al., 2017; Lee et al., 2002; Torén et al., 1996). The health hazardor risk surrounding the workplace of paper industries has previouslybeen reported to include risk of malignant disease, lung cancer, skinproblems, respiratory disease, autoimmune and cardiac conditions(Torén et al., 1996). However, during the last 15–25 years, the pulpand paper industry has made huge efforts to avoid occupational healthhazards by reiterating the processes and decrease their possible nega-tive impact (Hubbe et al., 2016). Nevertheless, chlorine, sodium hypo-chlorite, and chlorine oxide are indeed used in the paper and pulpprocesses in certain countries (Kumar et al., 2020a, b, c). The exploita-tion of chlorine-based chemicals in the bleaching process leads to or-ganochlorine compounds being produced from this step, and manychlorinated phenols indeed have adverse effects on human health(Table 1).

EDCs are a significant class of known chemicals that can interferewiththe natural hormonal systemof humans and animals. These effects on thehormonal system are either hyper or hypo, and as a result, various medi-cal conditions and deformitiesmay occur in the fetus development (Vilelaet al., 2018). Some environmental chemicals or pollutants that act as EDCinclude phthalates, bisphenol, and alkylphenols, which are all substantialwastewater components that people come into contact with daily(Jambor et al., 2018). The EDCsmay emerge from various agricultural, in-dustrial, and household sources and, as a result, reach our drinking waterand, ultimately, humans (Gelbke et al., 2004). It is uncertain if effluents ofpaper mills may contain steroidal estrogens e.g. 17β-E2,17β-E2, whichmay cause serious human reproductive disorders, but steroidal estrogenshave been detected at sites close to large wastewater treatment facilities(Adeel et al., 2017). Beyond reproductive toxicity, the development ofbreast cancer, prostate cancer, potentially negative neuroendocrine ef-fects, harmful metabolic and cardiovascular effects are key problematicfeatures of EDCs in humanphysiology (Sigman et al., 2012). Data froman-imal models, human clinical studies, and epidemiological studies indicateEDCs as an emerging environmental health hazard. Beyond steroidal es-trogens, including the synthetic estrogen ethinyl estradiol (Adeel et al.,2017), the problematic chemical compounds suspected to be EDCs and/

Fig. 3.Negative environmental consequences and hazardous impacts on humanhealth frompolor cause human developmental deformities.

6

or which may have cancerogenic effects include alkylphenols (4-octylphenol; 4-nonylphenol), nonylphenol, octylphenol, bisphenol alongwith its alternatives and phthalates (Calafat et al., 2008; Kasahara et al.,2002; Nimrod and Benson, 1996). Some known pollutants, includingchlorophenols thatmay be present in industrial paper and pulpwastewa-ter and their associated human disease/medical conditions are summa-rized in Table 1.

The human homeostasis systemmight be altered by environmentalexposure to environmental endocrine disruptors (EEDs). Animalmodel-based studies and other clinical observations and epidemiologi-cal studies have reported and suggested that EEDs are potentialendocrine-disrupting compounds that cause severe human medicalconditions and affect key functions in the human system, includingthe nervous system, reproductive system, thyroid, cancer, lungs, andmaymoreover induce obesity. Themale reproductive systemanddevel-opment, female reproduction and development, thyroid function, obe-sity, and diabetes are the most significant abnormalities caused byEEDs (Ropero et al., 2008; Sigman et al., 2012). A diagrammatic repre-sentation of human health hazards frommultiple environmental pollut-ants (Exposure of EEDs and its path to toxic endpoints) is shown inFig. 3.

4. The effluents of the paper industry: environmental impact andimplications

The adverse effects of a wide variety of toxic compounds (phenolics,lignin-derivatives, guaiacol, and heavymetals) present in effluents gen-erated from the different stages of the papermaking process (Hubbeet al., 2016) also include undesirable environmental effects, which con-tribute to a critical concern for the toxicity of thewater. Aquatic toxicityand impacts on the food chain have been identified (Shi et al., 2016) andseveral plantmodel systemshave been evaluated for possible hazards ofwastewater-mediated toxicity in different endpoints (Yu et al., 2019).Haq et al. (2016). Such toxic compounds have shown the phytotoxicityand cytotoxicity triggered by papermill wastewater on plantmodel sys-tems. For phytotoxicity research, in particular two plant model systems

lutants fromwastewaters. Certain pollutants can trigger undesirable endocrine effects and/

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

have been examined (Vigna radiata, and Allium cepa) to assess the pos-sible toxicity under specific environmental conditions in laboratory ex-periments. Papermill consequences in the Allium cepa root tip cellsappear extremely problematic involving inducing chromosome aberra-tion (genotoxicity). Nath (2016) reported morphological and hemato-logical effects on fish species Amblyceps mangois. Moreover,contamination from the paper industrywas anemic to fishes (hemolyticdisease) (Nath, 2016). A new study concludes that the highly toxic ef-fects of papermill effluents on Cyprinus carpio L. induced developmentaland lethal impact on the organs, including the gills and fins (Dey et al.,2018). Abhishek et al. (2017) reported that Kraft lignin as an active in-gredient of papermill effluents causes acute toxicity, as evaluated by re-active oxygen species generation and a cytotoxicity assay on humankeratinocyte (HaCaT) cell line (Abhishek et al., 2017). A diagrammaticillustration of wastewater-induced toxicity on the model system isshown in Fig. 4.

5. Current concerns and need for bioremediation

Environmental pollution is a major cause of significant damage tothe environment in today's global context. Paper industries contributeconsiderably by emitting various hazardous compounds into the envi-ronment through effluents. Phenolic and chlorinated contaminants ap-pear to be the most dangerous and complicated, owing to theirrecalcitrant and slow degradation potential (Azubuike et al., 2016).Enzyme-mediated bioremediation is a promising approach because en-zymes in their nature can selectively catalyze the conversion of many ofthe problematic compounds, even if the compounds are present in thewater at modest concentrations for “chemical reaction”. As mentionedearlier, the ligninmodifying enzymes are promising biocatalysts for sus-tainable mitigation of various pollutants of concern as these enzymeshave the potential to degrade a wide variety of lignin, methoxylatedcompounds, phenol, polyphenol, EDCs, and non-phenolic compoundsin an eco-friendly manner. Enhanced catalytic potential and productionof lignin-modifying enzymes may be achieved with enzyme

Fig. 4. Hazardous nature of paper industry effluents. Toxicity effects have been tested expegenotoxicity (chromosomal aberration), and cell lines based toxicity (cytotoxicity).

7

immobilization (Zdarta et al., 2019) and via engineered microbes(Azad et al., 2014; Dvořák et al., 2017).

5.1. Conventional bioremediation approaches for pollutants mitigation

Bioremediation is a promising practice wherein natural resourcessuch as bacteria and plants are used in an “eco-friendly” way to elimi-nate toxic organic pollutants (Tekere, 2019). The current bioremedia-tion strategies are focused mainly on biodegradation and thisapproach involves the complete elimination of harmless organic toxicsubstances from a highly contaminatedmediumor site. Many biologicaldegradation processes and pathways have been reported towork, eitherin the presence or absence of oxygen (Ghattas et al., 2017; Ronen andAbeliovich, 2000; Wang et al., 2019). Bioremediation research focuseson enhancing the strength of the remediation process by supplying op-timum concentrations of biocatalysts, chemicals and nutrients, usuallyincluding oxygen, necessary for the degradation and detoxification oftoxic components through microbial metabolism and/or enzymaticconversion (Adetutu et al., 2015).

Microbial assisted pollutant remediation involves usingmicroorgan-isms to either completely degrade toxic compounds into water and car-bon dioxide (organic pollutants) or to catalyze their conversion into lesstoxic forms (Malla et al., 2018). Because of its low cost and biology-based approach, this technology provides an efficient alternative to con-ventional chemical treatment methods (Kang, 2014). Bioremediation isthus considered an economical, versatile, effective, and environmentallysustainable solution compared to physical and chemical approaches totreat various environmental contaminants (Jeon and Madsen, 2013).Several remediation approaches are based on a bacterial-derived enzy-matic system, some are bioreactor based, and a few others includeplant-based approaches (see phytoremediation section). Using abacterial-mediated remediation strategy, the in situ or ex situmitigationof pollutants is implemented to clean up an affected site from contami-nants (Ali et al., 2013; Baric et al., 2014). In situ infers that the bioreme-diation occurs directly at/within the contaminated site. At the same

rimentally on plant systems (Vigna radiata, Allium cepa), evaluating the phytotoxicity,

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

time, ex situ implies that the microbial clean up may be applied off-sitefrom the contamination location. In situ, remediation is considered slowand frequently difficult in the natural environment to control and opti-mize various bioremediation parameters. In this context and ex situ re-mediation, it is advantageous to use specially designed bioreactors toboost remediation. Bioreactors have been designed for use in bioreme-diation processes to achieve the optimum conditions, including aera-tion, microbial growth, and biodegradation to meet the variousbioremediation goals. The bioreactors designed for bioremediation in-clude packaged, stirred tanks, airlift, slurry phase, partitioning phase re-actors are reported to be used in bioremediation of different organicpollutants (Pathak et al., 2020).

Numerous bacterial species producing lignin modifying enzymeshave been described over the last decades, and this type of enzymeshave been studied to remove lignin, chlorinated lignin, and organic phe-nol and chemicals that cause endocrine disruption in human (Bilal et al.,2019; Falade et al., 2018; Grelska and Noszczyńska, 2020). A newer per-oxidase enzyme has been recognized as a dye decolorizing peroxidase.As will be discussed later, this enzyme shows particular promise to beused as a biocatalyst for the removal of a range of toxic pollutants inwastewater. This enzyme acts on various substances, including;lignin-derivatives, dyes, and EDCs compounds (Brissos et al., 2017).Some important well-known microorganisms for lignin-modifying en-zyme production have been described in Table 2 and lignin compounds(lignin model compounds) that have been studied are listed in Table 3.Fig. 5 explains traditional bioremediation techniques in the treatment oflignin derivatives, phenolics, EDCs, and complex pollutants.

5.1.1. BiostimulationThis form of bioremediation strategy is related to promoting indige-

nous micro-organisms by injecting relevant nutrients on-site (soil andgroundwater). It tends to focus on stimulating the natural or indigenousmicroorganisms, whether bacterial or fungal communities. Firstly, byproviding inorganic nutrients, growth supplements, and trace minerals,secondly, through other environmental conditions such as pH, temper-ature, and oxygen to enhancing their metabolism and metabolic path-way. The inclusion of small amounts of pollutants can also serve as astimulant by switching on the enzyme's operons for bioremediation. Ni-trogen, phosphorus, and carbon are all necessary for this type of biore-mediation, that to our knowledge is not currently in use or consideredused industrially.

5.1.2. BioaugmentationThe bioaugmentation approach concerningwastewater bioremedia-

tion relies on that a particular microorganism is added to the wastewa-ter, and that the ensuing microbial growth can increase the rate ofpollutant degradation. Accelerating population growth and improvingnatural microbial degradation, using microbes that preferably feed oncontaminated sites, is a crucial feature of the bioaugmentation concept.It can be used to eliminate and alter micro-organisms, such as ethylene

Table 2Detailed potential lignin-modifying enzyme producers acting on different substrates, incl. mod

Bacterial species Strain Acting s

Rhodococcus jostii RHA1 ABTS, soThermobifida fusca YX Kraft ligBrevibacillus agri RJH-1 LigninEnterobacter lignolyticus SCF1 Lignin, nSerratia liquefaciens LD-5 Kraft ligEnsifer adhaerens NWODO-2 Lignin cRaoultella ornithinolytica OKOH-1 Lignin cKlebsiella pneumoniae NITW715076 Lignin, oStaphylococcus lentus SB5 Kraft ligPaenibacillus glucanolyticus SLM1 LigninBacillus subtilis KCTC2023 Lignin mPseudomonas putida MET94 ABTS

8

and chloride, that are not toxic (Cavinato et al., 2017). Natural or indig-enous microbial species are usually not feasible to rapidly break downpollutants of concern. Hence, DNA manipulation or genetically modi-fied/engineered microorganisms have been designed to promote moreefficient and robust degradation of pollutants (Pieper and Reineke,2000; Sayler and Ripp, 2000). However, despite this goal having beenpreceded for decades, there are still no full-scale applications (Janssenand Stucki, 2020), probably due to technical, economical, and ethical ob-stacles to the release of engineeredmicroorganisms (Deeba et al., 2018).

5.1.3. Microbial bioreactors in bioremediationBioreactors are used to treat contaminated soil andwater in meticu-

lous and efficient processes, the point being to convert the contami-nated media (e.g. wastewater rich in contaminants) into less toxiccompounds via promoting a sequence of biological reactions (Tekere,2019). Because temperature, pH, nutrient levels, and agitation can bemeasured in the reactors, microbial activity, and thus contaminant deg-radation, can be augmented (Jesitha andHarikumar, 2018; Pandey et al.,2009; Robles-González et al., 2008). Microbial bioreactors have beenimplemented in several laboratory and pilot bioremediation studiesfor different contaminants (Chikere et al., 2012; Pino-Herrera et al.,2017; Tekere et al., 2005). Flexibility in bioreactor design for variousprocesses and remediation applications makes bioreactors preferablefor bioremediation (Azubuike et al., 2016). The design should considerhigh cell biomass growth, nutrient supply, and waste removal fromthe system. The bioreactor technique has been practiced for effectiveuse for organic pollutant remediation at a few underground leakingstorage tanks at industrial sites (Iorhemen et al., 2016; Lone et al., 2008).

5.1.4. PhytoremediationThe use of plants tomitigate or eliminate inorganic and organic con-

taminants from the environment offers a practical, “clean and green,”environmentally friendly, low-cost, and environmentally friendly tech-nology (Pilon-Smits and LeDuc, 2009). Phytoremediation is a strategy ofbioremediation employing designated plants (sometimes in combina-tion with microbes) to remove, transfer, stabilize and/or eliminate soiland groundwater contaminants. The phytoremediation mechanismoften involves several other mechanisms, i.e. phytodegradation,phytostabilization, phytoaccumulation, rhizofiltration, etc. Generally,phytoremediation removes pollutants or converts pollutants into theirsimplest or less toxic form (Saxena et al., 2019). Several plants can ex-tract and concentrate on certain toxic elements from the environment,thereby providing a permanent remediationmethod. Phytoremediationis commonly recognized as a cost-effective technology for environmen-tal restoration (Lone et al., 2008). According to the environment andtypes of contaminants, different phytoremediation technologies areavailable to performbioremediation (Malla et al., 2018). Volatile organiccompounds have been reported to be eliminated from the environmentand be assimilated with plants (Pariselli et al., 2009). Phytoremediationfor wastewater is a plant-mediated emerging bioremediation

el lignin compounds and industrial dyes.

ubstrate References

ftwood lignin (Singh et al., 2013)nin, lignin model compounds (Rahmanpour et al., 2016)

(Hooda et al., 2015)on-phenolic lignin compounds (Shrestha et al., 2017)nin (Haq et al., 2016)ompounds, indicator dyes (Falade et al., 2017)ompounds, indicator dyes (Falade et al., 2017)rganic substrate (Gaur et al., 2018)nin (Baghel and Anandkumar, 2019)

(Mathews et al., 2016)odel compounds, azo dyes (Min et al., 2015)

(Santos et al., 2014)

Table 3Overview of chemical structures and elementary attributes of primary lignin monomers (p-coumaryl alcohol, coniferyl alcohol, sinapyl alcohol) and lignin model compounds.

Lignin monomers and ligninmodel compounds

Chemical structure IUPAC name Molecularweightg/mol

Molecularformula

References

p-Coumaryl alcohol 4-[(E)-3-Hydroxyprop-1-enyl]phenol 150 C9H10O2 (Sitarz et al., 2016)

Coniferyl alcohol 4-[(E)-3-Hydroxyprop-1-enyl]-2-methoxyphenol 180 C10H12O3 (Hong et al., 2016)

Sinapyl alcohol 4-[(E)-3-Hydroxyprop-1-enyl]-2,6-dimethoxyphenol 210 C11H14O4 (Harman-Wareet al., 2017)

Syringol 2,6-Dimethoxyphenol 154 C8H10O3 (Kawamoto, 2017)

Mequinol 4-Methoxyphenol 124 C7H8O2 (Xiao and Kondo,2020; Xu et al.,2019)

Cathecol Benzene-1,2-diol 110 C6H6O2 (Xu et al., 2019)

Guaiacol 2-Methoxyphenol 124 C7H8O2 (Ravi et al., 2019)

Methoxybenzene Anisole 108 C7H8O (Zhang et al., 2014)

Methylhydroquinone 2-Methylbenzene-1,4-diol 124 C7H8O2 (Granja-Travezet al., 2020)

Syringyl alcohol 4-(Hydroxymethyl)-2,6-dimethoxyphenol 184 C9H12O4 (Kim and Ralph,2005)

Veratryl alcohol (3,4-Dimethoxyphenyl)methanol 168 C9H12O3 (González-Riopedreet al., 2013)

Dimer lignin model compound:guaiacylglycerol-β-guaiacylether (β-O-4)

1-(4-Hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol

320 C17H20O6 (Perna et al., 2018;Rodríguez et al.,2019)

Trimer lignin model compound:syringyl-β-O-4-syringyl-β-O-4sinapyl alcohol

2‐[4‐(2‐{4‐[(1E)‐But‐1‐en‐1‐yl]‐2,6‐dimethoxyphenoxy}‐1,3‐dihydroxypropyl)‐2,6‐dimethoxyphenoxy]‐1‐(4‐hydroxy‐3,5‐dimethoxy-phenyl)propane‐1,3‐diol

667 C34H44O13 (Awasthi et al.,2015; Flourat et al.,2019)

Tetramer lignin modelcompound: guaiacyl β-O-4syringyl β-β syringyl β-O-4guaiacyl

2‐[4‐(4‐{4‐[3‐Hydroxy‐3‐(4‐hydroxy‐methoxy-phenyl)‐2‐(hydroxyl-methyl)propyl]‐3‐(hydroxymethyl)‐5‐methoxyphenyl}‐hexahydrofuro[3,4‐c]furan‐1‐yl)‐2,6‐dimethoxy-phenoxy]‐1‐(3‐methoxy-phenyl)propane‐1,3‐diol

793 C43H52O14 (Awasthi et al.,2015; Mester et al.,2001)

(continued on next page)

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

9

Table 3 (continued)

Lignin monomers and ligninmodel compounds

Chemical structure IUPAC name Molecularweightg/mol

Molecularformula

References

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

technology, where plants utilize contaminated industrial wastewaterand groundwater to eliminate toxic pollutants (Stefanakis andThullner, 2016). Recently many transgenic plants have been reportedfor different forms of phenolic and chlorophenol pollutants eliminationusing phytoremediation (Cherian and Oliveira, 2005; Eapen et al., 2007;James and Strand, 2009; Macek et al., 2008; Wang et al., 2004). Plantroots may produce potent redox enzymes (oxidoreductases) such asperoxidases, encompassing non-specific oxidation polymerization reac-tions as a base for plant cell wall growth. These enzymesmay also play asignificant role in reactions for promoting detoxification and play a rolein phenol and chlorophenol removal. Laboratory studies have been per-formed to examine pollutants reduction through phytoremediationwith different plants, for pulp and paper wastewaters (Kumar andChopra, 2016). Recently phytoremediation has been implemented andreported for use in removing pollutant load from paper and pulp indus-tries (Kumar et al., 2020a, b, c). However, although phytoremediationtechnology has shown enormous promise, large scale field studies arescant (Beans, 2017).

Fig. 5. Explanatory illustration of bioremediation processes via use of different advanced bioremHazardous compounds from wastewaters can be treated by employing all described techniqubioremediation.

10

Further research is also needed to ascertain the fate of various com-pounds in the plantmetabolic cycle to ensure that no toxic or hazardouschemicals contribute to the food chain. Also, the disposal of harvestedplants can be bothersome if they have elevated heavy metal levels.The application of phytoremediation is typically restricted to areaswith low contaminant levels and contamination of shallow soils,streams, and groundwater.

5.2. The core advantages of bioremediation

▪ It is a natural process, time-saving, as a waste treatment methodsuitable for harmful content. Microbes are capable of pollutant deg-radation, and when the microbe has been properly selected, thenumber of microbes will be rising when there is a pollutant. Thetreatment residues are usually harmless or less hazardous. The pro-cess avoids the transfer of waste off-site and potential hazards to theenvironment and human health that could arise during the catabo-lism of pollutants.

ediation technologies:microbial, biostimulation, bioaugmentation, and phytoremediation.es. The lignin-modifying enzymes can be used in combination with microbially mediated

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

▪ It may be implemented efficiently and effectively and is more cost-effective than other conventional technologies used in hazardouswaste mitigation.

▪ It often contributes to mitigating the contaminants. Several hazard-ous compounds may be converted into harmless substances. Thischaracteristic also eliminates potential liability for the treatmentand disposal of contaminated materials.

▪ Nohazardous chemicals are usedwith thismethod. Added nutrients,especially fertilizers, activate and boost microbial growth. Bioreme-diation transforms dangerous substances into harmless substancesand gasses.

▪ Pollutants are destroyed, not just transferred to various environ-mental media.

▪ Non-intrusive, which may allow continued use of the site.▪ Relatively easy to implement.

5.3. The key disadvantages of bioremediation

▪ Not all hazardous substances can be degraded quickly andcompletely

▪ There are some issues regarding the persistent or toxicity of biodeg-radation products over the relative compound.

▪ Unique biological processes are often crucial site factors. The exis-tence of microbial communities needed for achievement in suitableenvironmental growth conditions and adequate nutrient and con-taminant levels.

▪ From bench and pilot studies, it is difficult to extrapolate into full-field operation.

▪ Research is necessary to develop and create technologies for the bio-remediation of sites with complicated mixtures of pollutants, notsimilarly distributed in the environment. Solids, fluids, and gassescan be contaminants.

▪ It is often slower than other treatment alternatives.▪ Uncertainty in the regulatory framework persists concerning accept-able bioremediation performance criteria. No accepted definition of“clean” is given. It is challenging to evaluate bioremediation perfor-mance.

▪ No complete information can be obtained, in terms of toxicity andenvironmental fate of all transformed compounds, that is a signifi-cant flaw in bioremediation. Exploratory and preliminary investiga-tive studies have been been implemented by in silico approaches inbioremediation (described in Section 7.1).

6. Lignin-modifying enzymes for sustainable mitigation of lignin,phenolics, and a wide variety of pollutants

Microbially derived ligninmodifying enzymes have been studied ex-tensively for their catalytic potential concerning the removal of pollut-ants. As already indicated in the introduction, the enzymes includelaccases, LiP, MnP, VP, and dye decolorizing peroxidase. Based on thecatalytic mechanism, it is noted that these enzymes can be classifiedinto two categories: 1. laccases that use O2 as oxidant (electron accep-tor) in the enzyme-catalyzed reaction, not requiring H2O2 for reactionand 2. peroxidases, which are H2O2 dependent.

The LiPs are involved in the oxidative degradation of lignin by cata-lyzing bond breakage, and may also degrade lignin-derived oligomers,including non-phenolic and phenolic compounds (Lundell et al., 2010;Qi-He et al., 2011).

LiP, VP, and DyP act on diols and sulfonic substituents on benzenerings and non-phenolic lignin compounds, whereas laccase and MnPcan catalyze the oxidation of available phenolic components of lignin di-rectly, but laccases cannot directly catalyze bond breakage in lignin un-less mediator compounds are present (Munk et al., 2015). Bacteriallaccases and peroxidases are structurally different from the most com-mon fungal counterparts, and the fungal-derived laccases and

11

peroxidases also appear to be more studied than the bacterial ones.However, a few bacterial species (Firmicutes, Gamma proteobacteria,and Actinobacteria, as well as Rhodococcus and Streptomyces) expressperoxide-dependent peroxidases, including DyP enzyme types (deGonzalo et al., 2016). DyPs have been found to oxidize a range of diversesubstrates, including lignin, lignin-derived compounds, phenolic com-pounds, and various synthetic dyes (Brissos et al., 2017; Colpa et al.,2014); and an engineered variant (with an asparagine-to-alanine sub-stitution (N246A) of the Rhodococcus jostii bacterial dye decolorizingperoxidase is able to efficiently catalyze the transformation of hard-wood Kraft lignin substances (Singh et al., 2013; He et al., 2017). Con-templation of the data indicate that among the lignin modifyingenzymes, laccase and LiP appear to be the most promising biocatalystsfor wastewater remediation, but DyPmay also have bioremediation po-tential due to its broad substrate use but has been less studied. These en-zymes act broadly on non-phenolic lignin compounds, various dyes, andseveral endocrine disputing compounds (Blánquez et al., 2019; Faladet al., 2017; Pramanik and Chaudhuri, 2018; Wang et al., 2018). A com-parative catalytic pattern of ligninmodifying enzymes is shown in Fig. 6.

6.1. Plant based peroxidases for pollutants remediation

Peroxidases from plants have received some interest in the past fortheir ability to eliminate phenolic pollutants from synthetic and indus-trialwastewater (González et al., 2008; Kurnik et al., 2015). Plant perox-idases belong class III peroxidases, and their catalytic mechanism issimilar to that of standard peroxidases (Chagas et al., 2015). The plantperoxidases include soybean peroxidase, horseradish peroxidase, andturnip peroxidase (Qayyum et al., 2009). Horseradish peroxidase waspreviously considered a most promising plant peroxidase candidatefor wastewater contaminated with phenolic compounds (Ashraf andHusain, 2010), but appears to be overtaken by other peroxidases (andmicrobially produced laccases). Enzyme immobilization has been ex-plored to improve enzyme robustness and biocatalytic efficiency:Akhtar andHusain used various immobilized plant-derived peroxidasesfor removal of phenolic pollutants (Akhtar and Husain, 2006). Qayyumet al. (2009) reported enzyme-catalyzed degradation and transforma-tion of numerous PAHs, PCBs, organochlorines, phenolic compounds,and several dyes with immobilized plant peroxidase (Qayyum et al.,2009). Kurnik et al. (2015) performed a similar study and reported ahigh phenol decontamination potential in industrial and syntheticwastewaters (95% phenol removal efficiency) of a potato pulp-derivedperoxidase (Kurnik et al., 2015). Nevertheless, the application of plantderived enzymes appears to have been overtaken by microbially pro-duced enzymes that can be recombinantly produced easier and cheaperthan plant peroxidases, although certain plant peroxidase have been re-ported recently for efficient removal of phenols (see Section 6.3).

6.2. Microbial biodegradation of lignin and its derivatives

High molecular weight (HMW) technical lignin is present in thepaper industry's wastewater as a contaminant (Baghel et al., 2020). Acomplex chemical structure, composed of stable biological bonding, isresistant to microbial degradation (Chen et al., 2012). However, severalmicroorganismswith lignin degradation potential, including fungi, acti-nomycetes, and bacteria, have been found in nature (Janusz et al., 2017;Kirby, 2005). White-rot and brown-rot fungi have been thoroughlystudied for lignin degradation over the past few decades (Kirk andFarrell, 1987).

As persistent organic contaminants, both lignin and lignin-derivedcompounds can persist in the environment and trigger environmentalhazards. Lignin-based pollutants in wastewater from the paper & pulpindustry are also the primary source of pollution. It should also be min-imized to eliminate the risks (Haq et al., 2017; Vashi et al., 2018). Enzy-matic lignin degradation has been mostly investigated with differentligninmodel compounds rather than natural lignin and its components.

Fig. 6. Comparative schematic lignin degradation reaction representation of ligninmodifying enzymes. Laccasemediated-lignin catalysis takes place during O2 consumption and does notrequire H2O2. Peroxidases (LiP, MnP, VP, DyP) require H2O2 for oxidative biocatalytic cleavage of lignin polymers.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

As outlined above, in natural lignin the C\\O linkages, especially(β–O–4) type ether bonds and C\\C type linkages are prevalent. Still,different technical lignin-derived compounds are generated from thepaper pulping process (Kraft, soda, organosolv, sulfite, hydrolysed).Specifically, the following 6–7 types of inter-unit linkages in technicallignin are found; (1) 1-phenyl-2 phenoxyethanol; (2) pinoresinol,(3) bibenzyl, (4) benzofuran, (5) diphenyl ether, and (6) biphenyl,which may represent β–O–4, β–β, β–1, β–5, 4–O–5 and 5–5 type link-ages respectively (Guadix-Montero and Sankar, 2018). Many lignin-modifying enzymes have been demonstrated able to catalyze breakageof these bonds in lignin model compounds, and they can also catalyzethe oxidation of pollutant phenol compounds from the paper industry(Table 4).

Certain lignin modifying peroxidases may act on organic pollutantsby cleaving of β–O–4 (ether linkage), generating free radicals, usingone-electron oxidation. Generated cation radicals can spontaneouslyundergo chemical reactions, including hydroxylation or C\\C cleavage,leading to hydrophilic products (Bosque et al., 2017).

6.3. Biocatalytic biodegradation of phenolic compounds

The ligninmodifying enzymes or peroxidases have been reported forthe bioremediation of phenolic contaminated wastewater (phenols,cresol, and chlorinated phenols), emerged from industrial processing(Ong et al., 2011). Peroxidases, including LiP and horseradish peroxi-dase, have been reported as efficient tools for transforming pentachlo-rophenol at different concentrations in the presence of H2O2 (Kimet al., 2006; Zhang et al., 2007). MnP is an extracellular enzyme pro-duced by various microorganisms and its ability to eliminate phenoliccompounds by oxidative catalysis relies on a mechanism that involvesoxidation of Mn2+ into Mn3+ using one electron, and H2O2 as co-substrate, hence its name (Hakala et al., 2006). In recent years, variousplant peroxidase mediated detoxification of phenol from synthetic andindustrial wastewater has been reported in laboratory studies. Variousplant peroxidases including, turnip, potato, soybean, gourd, rapeseed,etc. have been reported for the elimination of a wide variety of phenols

12

and phenolic compounds, including 2,4-dichlorophenol, guaiacol, m-cresol, p-cresol, o-cresol, anisole, resorcinol, catechol, pyrogallol, hydro-quinone, and veratryl alcohol (Kurnik et al., 2015; Kurnik et al., 2018).

6.4. Biodegradation of endocrine-disrupting chemicals

Discharge of wastewater from the paper sector often contained nu-merous phenolic derivatives, and endocrine-disrupting chemicals(EDCs) reported as harmful in several respects to human health. EDCsare the chemical compounds that interact with the endocrine system,impacting developmental, reproductive, and neurological by causingnegative effects in humans and animals (Cooke et al., 2013). Differenttechniques are involved and reported to eliminate EDCs fromwastewa-ter exploiting enzymatic treatmentwithmicrobially derived laccase andperoxidase (Falade et al., 2018; Grelska and Noszczyńska, 2020). How-ever, it has been documented that traditional wastewater treatment isless effective in removing such EDCs; meanwhile, peroxidases havethe potential for efficient removal of EDCs (Zheng and Colosi, 2011).Their substrate versatility can catalyze reactions that eliminate or re-duce major environmental pollutants, such as chloroanilines and aro-matic polycyclic hydrocarbons from various sources (Harayama,1997). The assessment of the removal of phenolic EDCs has been re-ported in recently reported studies exploiting plant peroxidase.Among such studies, several phenolic compounds bisphenol-A (BPA),2,4-dichlorophenol (2,4-DCP), 4-tert-octylphenol (4-t-OP), and penta-chlorophenol (PCP) were successfully removed, exploiting plant perox-idase(Reis et al., 2014). The subsequent experiments of the abovestudies showed that a significant amount of EDCs were removed byusing plant-based peroxidase (POs) assisted treatment (Reis et al.,2014). In a similar study, few selected endocrine-disrupting chemicals,including bisphenol-A, along with some estrogenic compounds (es-trone (E1), 17β-estradiol, and 17α-ethinylestradiol) from real and syn-thetic wastewater were removed exploiting VP by use of a two-stagesystem (Taboada-Puig et al., 2015). The degradation rates of EDCs (es-trone, 17β-estradiol, and 17α-ethinylestradiol) were reported to be inthe range of 28–58 μg/(L·min) (Taboada-Puig et al., 2015).

Table 4Molecular properties of lignin-modifying enzymes, based on a representative PDB ID for each type of enzyme: for each enzyme type, the number of constituent amino acid residues, mo-lecular weight, and co-factor metal type are given.

Lignin-modifying enzyme PDB ID Constituent amino acids residues Molecular weight Co-factor Reference

Lignin peroxidase 3Q3U 338 35,185 Da Fe (Miki et al., 2011)Dye decolorizing type peroxidase 5VJ0 318 35,370 Da Fe (Shrestha et al., 2017)Manganese peroxidase 3M5Q 357 37,455 Da Mn (Sundaramoorthy et al., 2010)Laccase 3PPS 604 66,533 Da Cu (Kallio et al., 2011)Versatile peroxidase 5FNB 331 34,641 Da Fe (Sáez-Jiménez et al., 2016)

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

6.5. Biodegradation of chlorinated phenolics

As outlined above (Table 1), the pulp and paper mill effluentsmay contain substantial levels of potentially hazardous chlorinatedcompounds (Jayaraj et al., 2016; Thacker et al., 2007) that typicallyform during the pulp bleaching process (Barber et al., 2020). Variouslignin modifying enzymes have been reported to reduce organochlo-rine from such wastewater (Garg and Tripathi, 2011; Karigar andRao, 2011; Upadhyay et al., 2016). Peroxidases aided wastewaterpollutant removal is an eco-friendly and highly productive way to re-move recalcitrant and persistent contaminants (Bilal and Iqbal,2020). Martínková et al. (2016) reported the bioremediationpotential of phenolic compounds (phenols, bisphenols, cresols,alkylphenols, polyphenols, naphthols, and halogenated (bis)phe-nols) by use of Basidiomycota (Martínková et al., 2016). Similarly,Rubilar et al. (2008) reviewed the transformation ability ofligninolytic white-rot fungi for chlorinated phenolic compounds(Rubilar et al., 2008), whereas Paz et al. recently reported the abilityof Bacillus aryabhattai to catalyze biotransformations of phenoliccompounds (Paz et al., 2019).

7. Recent advances in bioremediation for pollutant remediation

Bioremediation provides an effective, eco-friendly, and effectivewayto combat wastewater pollution concerns, including the discharge ofphenolics and lignin-derived pollutants to the environment (Hlihoret al., 2017). Several microbial species, including bacteria and fungi,have shown their potential in bioremediation of relevant pollutants bysecretion of potential lignin modifying enzymes, and bacterial-mediated bioremediation has longproven an effective and low-cost sus-tainablemitigation strategy for removal of pollutants fromwastewaters(Raj et al., 2014). Several bacterial species, including; Pseudomonas sp.Pycnoporus, Agrobacterium, Bacillus, Rhodocococcis erythropolis,Rhizobium sp. have thus been reported useful for biodegradation ofpollutants from the environment (Kang, 2014; Kumar et al., 2013;Urgun-Demirtas et al., 2006). However, the field trials have not alwaysbeen successful, pointing at the need for further development.

In order to maximize the degradability and enhanced degradationrate of bioremediation approaches, there has recently been substantialprogress via the use of advanced biotechnology methods, includingthe development of genetically modified organisms, metabolic engi-neering, and e.g. use of in silico modeling and prediction approachesand protein engineering of enzymes to target and enhance efficiencyand robustness (Aukema et al., 2017; Gauchotte-Lindsay et al., 2019).In the recent few years, genetically modified organisms have beenconstructed to increase the degradability of pollutants for the biore-mediation of numerous carcinogenic, phenolic substances, heavymetals, and so on (Dvořák et al., 2017; Liu et al., 2019; Rucká et al.,2017; Sanghvi et al., 2020; Tay et al., 2017). In addition to geneticallymodified (or engineered) microorganisms, it deserves to be men-tioned that other innovative techniques are also currently beingused for the clean-up of pollutants and restoration of ecologicalniches. These techniques include, for example, photocatalysis andadvanced oxidation processes (AOPs) that have been promoted fordifferent organic pollutant removal from wastewater (Carbajoet al., 2017; Poulopoulos et al., 2019).

13

7.1. In silico approaches, molecular modeling, and degradation pathwayprediction

In silico bioremediation, the approach integrates various computa-tional techniques, including molecular docking, molecular dynamicssimulation, homology modeling, degradation pathways predictions,etc. (Singh et al., 2020a; Singh et al., 2021a, b). Conventional bioremedi-ation techniques are quite a time talking and long-term strategies forremediating various phenolic, lignin-based pollutants. Sometimes tradi-tional remediation techniques based on oxidoreductase may fail to per-form mitigation of organic pollutants effectively. Extrinsic factors,i.e., temperature, pH, nutrition, etc. are responsible for failure or slowerdegradability. Without knowledge of complete bio-transformed com-pounds from bioremediation, the environmental fate and toxicity pro-file of each transformed compound cannot always be determined byconventional bioremediation (Sanghvi et al., 2020). In silico bioremedi-ation approaches exploit and rely on various fields, including genomics,computational biology; proteomics; bioinformatics; molecular model-ing, molecular dynamics simulation, and a specialized algorithm forpathways prediction (Karp et al., 2011; Kleinman et al., 2014; Parentyet al., 2013). Such integrated techniques provide a quick insight into en-zyme and pollutants for their binding, catalysis, and degradation mech-anism. Such advances are highly useful to the virtual screening ofconcern pollutants, especially when conventional bioremediation failsto perform. In silico toxicology, part of predictive bioremediation pro-vides quick toxicity endpoints prediction in a sophisticated and time-savingmanner, which cannot be accomplished throughwet lab toxicityassays (Raies and Bajic, 2016; Rim, 2020; Singh et al., 2020a, b). In silicobioremediation approach is known for its potential as it is performed onspecialized computer systems; however, this approach simplifies theproblem to be further conducted in vitro and in vivo assays and makesit easier than traditional bioremediation (Aukema et al., 2017). Duringcatalysis, the actions of catalytic enzymes (oxidoreductases) can bemodeled and visualized through molecular dynamics simulation. Thistechnology can help predict the catalytic potential and binding patternof pollutants to enzyme proteins, and thus predict the potential for en-zymatic biodegradation (Chen et al., 2011). Besides, the amino acids in-volved in the catalytic mechanism in the active site of the enzyme, themolecular basis for activity, the binding mode of diverse substrates,and even quantitative structure-activity relations can be predictedthrough molecular docking (Liu et al., 2018; Mehra et al., 2018a;Mehra et al., 2018b), and such predictions can therefore serve to targetrational engineering of new enzymes for bioremediation of specific sub-strates and hence pollutants (Liu et al., 2018; Mehra et al., 2018b). Mo-lecular docking has indeed been applied to screen of enzyme catalyticbinding modes and enzyme-substrate affinities for laccase to differentlignin-derived phenolics (Mehra et al., 2018a; Mehra et al., 2018b)and was recently used in relation to remediation of industrial textiledyes (Srinivasan et al., 2019).

Degradation pathway prediction is another key computational ap-proach that can be exploited for predictive bioremediation or in silicobioremediation approach (Karp et al., 2011; Riaz et al., 2020). Usingthe PathPred pathway prediction tool/server developed by Kenehisaand coworkers (Moriya et al., 2010), environmental fate and degrada-tion pathways can be predicted for a series of target and enzymaticallytransformed compounds, and such pathway degradation modeling

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

can help predict the environmental fate and potential toxicity profile ofenvironmental pollutant chemicals (Moriya et al., 2010; Wackett,2013). The pathways prediction uses the biochemical reactions infor-mation already stored in the server, based on pre-existed availableknowledge from literature and databases (Moriya et al., 2010). The insilico approaches for bioremediation of organic pollutants are importantnovel techniques, which can help develop novel bioremediation strate-gies and even help select themost optimal enzymes for enhanced biore-mediation. Fig. 7 outlines the in silico-based bioremediation approachesto sustainable mitigation of environmental contaminants.

7.2. Protein engineering approaches

As alreadymentioned above, innate or natural bacterial-mediated bio-remediation processes for organic pollutants are effective strategies forcleaning-up industrial pollutants from the environment (Benjamin et al.,2019). Intrinsic and genetically engineered microorganisms can indeedmitigate such contaminants efficiently and quickly (Sayler and Ripp,2000). Wild type biocatalysts may require stabilization or, as mentionedabove,molecular improvement to target specific problematic compoundsto be efficient for practical bioremediation (Lendvay et al., 2003; Liu et al.,2019). Although stabilization may be accomplished by physical immobi-lization (as e.g. used by Zdarta et al., 2019),molecular evolution or proteinengineering provides an innovative opportunity to apply novel and so-phisticated biological materials to mitigate pollution (Singh et al., 2008).Until now, significant efforts have been directed at identifying,documenting, and understanding the catalytic capabilities and robustnessof laccases and lignin modifying peroxidases in relation to degradation ofspecific compounds (including pollutants) (Kallio et al., 2011; Kalyaniet al., 2016; Karigar and Rao, 2011; Kim et al., 2006; Mehra et al., 2018a,Mehra et al., 2018b; Miki et al., 2011; Min et al., 2015; Sáez-Jiménezet al., 2016; Santos et al., 2014; Singh et al., 2013). Protein engineering

Fig. 7. Illustrative explanation of the in silico approach in bioremediation. Expert systems or algoand toxicity of concern pollutants with different toxicological endpoints. Other techniques usedpathways prediction, and predictive toxicity. The predictions can help to plan remediation me

14

of enzymes is widely used in a range of processing industries to enhancee.g. the activity, robustness, or inhibitor resistance of enzymes. At thispoint, it is uncertain if protein engineered enzymes have been used inpractice for large scale pollutant bioremediation, but in agreement withthe perspectives outlined in a recent review (Mishra et al., 2020)we fore-see an increased emphasis on protein engineering in the near future todevelop efficient biocatalysts for pollutant elimination.

7.3. Genetically engineered microbes (GMOs)

Environmental management of environmental contamination bymicroorganisms is a feasible strategy to ensure environmental sustain-ability (Pieper and Reineke, 2000). Even though the natural or intrinsicbacterial species are best known for performing bioremediation pro-cesses to clean up various pollutants (PAHs, PCBs, pesticides, anddyes), either ex situ or in situ (Leigh et al., 2006; Sachan et al., 2019;Wang et al., 2018). However, the restoring rate to balance the perfectenvironment from natural bacterial species is relatively slow. Nearlyevery day, the pollutant loads are growing significantly from paper in-dustries and other pollution emitting industries. Thus, GMOs technol-ogy currently performed for pollutants of interest has been used tomitigate all these concerns (Singh et al., 2011). Microbial-based biore-mediation has received considerable global attention to reducing pollu-tion due to environmental-friendly, global acceptance, and reducedhealth hazards and genetically modified bacteria are gaining increasingattention for pollutant reduction in the field of environmentalrestructuring (Saxena et al., 2020). For GMO's development, four basicprinciple approaches have been proposed concerning the applicationin bioremediation (Jariyal et al., 2020): 1)modification of enzyme spec-ificity and affinity (see the previous section); 2) pathway constructionand regulation (as already outlined above); 3) bioprocess development,monitoring, and control; and 4) bioaffinity bioreporter sensor

rithmmediated processes use for prediction of degradation pathways, environmental fate,in predictive bioremediation include; molecular docking, molecular dynamics simulation,asures by understanding the fate and degradation paths of concern pollutants.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

applications for chemical sensing, toxicity reduction, and end analysis(Jariyal et al., 2020). Nevertheless, there is some concern that certain ge-netically engineered microorganisms are being introduced into the en-vironment, implying further delaying field-testing of these organismsuntil safety and environmental issues can be addressed.

7.4. Gene editing CRISPR aided approaches in bioremediation

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)is a newly identified gene-editing technique for cells and bacteria. Nu-merous bacteria have been edited for their gene/genome for diverse ap-plications (Behler et al., 2018; Donohoue et al., 2018; Liu, 2020; Tapscottet al., 2019). Due to its high degree of flexibility and accuracy in DNAcutting and pasting, it is now the globally accepted and widely usedtechnique for editing genes of interest. Gene editing has thus drawn sig-nificant attention in the scientific community due to its extraordinarycapabilities. This approach (CRISPR-Cas9) is thus being applied in agri-culture and human health for a vast number of applications, andgenome-editedmicroorganisms are being introduced in several sectors,even for designing edible probiotic microbes (Yadav et al., 2018) andhas recently been considered used in bioremediation (Jaiswal et al.,2019). In addition to applying CRISPR to microorganisms, plants mayalso be genome edited for improved tolerance of organic and inorganicpollutants in the environment (Saxena et al., 2020). Several plant ge-nomes have already been edited for applications/phytoremediation ofpossible hazardous contamination mitigation (Basharat et al., 2018;Bortesi and Fischer, 2015; Cherian and Oliveira, 2005; Yin et al., 2017;Zaidi et al., 2017). CRISPR technology could thus strengthen the naturalprocess of bioremediation without high risks and costs (Cheng et al.,2015; Khorsandi et al., 2018; Huang et al., 2019; Yadav et al., 2018). Ina recently published review, Basharat et al. (2018) reported aninteresting vision of a futuristic phytoremediation scenario based onCRISPR-mediated genome reprogramming of plants. In line with this vi-sion, we foresee that significant breakthroughs will be achieved on thebioremediation front not only using CRISPR-aided engineering butexploiting the selectivity and sustainability of biobased approaches ingeneral for the safe removal of pollutants from industrial wastewater.

8. Future perspectives

Although paper production relies on the use of renewable feedstockmaterial, the current processing practices create significant amounts ofwastewater that contains toxic pollutants that need to be removed forenvironmental and human health reasons.

The pulping and bleaching processes are the key steps wherein thechemical conversion of the lignocellulosicmaterial process occurs, nota-bly leading to modification and transformation of the chemical compo-sition of the lignin that is removed to manufacture the cellulose-richpaper. During such operations, technical lignin is abundantly producedas a by-product. Such technical lignin and several toxic compounds posea negative impact on the environment. The paper industry's by-products have been recognized as; lignin in different forms (Kraft lignin,soda lignin, organosolv lignin, hydrolyzed lignin, sulfonated lignin),phenolics, chlorinated, and several EDCs. Kraft lignin is the most fre-quent and abundant type of technical lignin resulting from large scalepulp and paper processing. Scientific studies have shown that Kraft lig-nin is a potentially toxic agent, as confirmed by various toxicology as-says, and genotoxicity and cytotoxicity assessments using cell lines. Inaddition to the toxicity of Kraft lignin, certain toxic compounds likechloro-lignins, sulfonated compounds, phenolics, and EDCs inwastewa-ter inflict harm to the environment. Many scientific studies have re-ported that hazardous compounds (dioxin, furan, chlorinated, andphenolic compounds) are also prevalent in wastewater from paperand pulp processing. These compounds trigger human endocrinedisorders andmay induce developmental deformities in the developingembryo. Bioremediation and more recently biocatalytic and enzyme-

15

assisted pollutants removal appear promising. Implementation ofnewly emerged technologies, integration of omics, and computationalbiology could be addressed the existing concerns andfill the gap for bio-remediation. Suggested implementation further may provide a directlook at the pollutant removal obstacles. The current critical analysishas revealed the current status and practices in bioremediation pro-cesses, but there are still many obstacles that could be reduced by takingthe following points into consideration:

1. Enhancing the production yields of the relevant bacterial orfungal-derived enzymes, current costs of enzyme production andlow availability is still a challenge for large scale implementation ofenzyme-based bioremediation.

2. Existing lignin-modifying strains have certain limitations and some-times fail to eliminate the target pollutant compounds. In the case ofchlorinated lignin, endocrine-disrupting chemicals, the wild typelignin-modifying microbial strain may not eliminate the compoundssufficiently fast or completely — the compounds are indeed toxic, sothe survival and robustness of the microbes may be a barrier. GMOsfor different pollutants degradation pathways associated with geneintegrations can be constructed to simplify the current multiple pol-lutant and enzymatic selectivity, and/or microbial bioremediationmay be combined with targeted enzymatic pollutant removalstrategies.

3. Available conventional bioremediation techniques are cost-effectivebut time-consuming. Enzymes can be engineered to efficiently con-vert target compounds and plant and microbes may be designed tointegrate different genes that promote certain pathways of degrada-tion and then eliminate different problematic pollutants, includingchlorophenols and EDCs. Targeted bioengineering for bioconversionscould be accelerated using novel biotechnologies such as predictivemolecular modeling, protein engineering for accelerated molecularprotein evolution of enzymes, cloning, and genome editing (CRISPR).These types of advanced biotechnology approaches are expected tosignificantly impact bioremediation and also help understand howthe biological systems respond to pollutants.

4. Establishing effective biobased remediation of pollutants may be ex-pedited by using targeted in silico approaches. The key in silicomethods include molecular docking, molecular dynamics simula-tions, degradation pathways predictions, and predictive toxicology.The use of these techniques can also advance the understanding ofthe environmental fate and potential toxicology of the converteddegradation compounds. Therefore, integration of predictive toxicol-ogy, predictive bioremediation tools/servers is recommended forachieving targeted bioengineering and maximum degradation. Con-sequently, sustainable, eco-friendly mitigation strategies, includingtargeted enzyme-based clean-up approaches could be introducedfaster to improve environmental protection and avoid health-hazardous compounds to be spread.

9. Concluding remarks and research trends

Lignin derivatives and chlorinated phenolic compounds are themostprevalent contaminants that end up in wastewater from paper produc-tion. The problematic compounds are mainly produced at the pulpingand bleaching stages. Several of these compounds are acutely toxic hav-ing adverse effects on plants (being phytotoxic), the aquatic system andthe overall ecosystem, and hence the environment. Some of the effluentcompounds can moreover trigger mutagenic and genotoxic effects, andsome of the polychlorinated compounds are even considered to beEDCs. To overcome those severe issues, several lignin modifying en-zymes, laccases, and peroxidases such as LiP, MnP, VP, and not leastthe more recently described DyPs are eco-friendly natural biocatalysts,which could eliminate a broad range of these environmental contami-nants, especially the phenolics. Other bioremediation approaches havealso been examined, but to our knowledge, none of these are in use in

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

practice at a very large scale. Newer computational biological pathwayprediction methods combined with molecular biology and enzymetechniques such as CRISPR technology, protein engineering, and/or im-mobilization technologies for enzyme stabilization provide new power-ful toolsets for developing efficient, sustainable, and robust enzymaticand biobased treatment methods. We anticipate and hope that thesebioremediation technologies will be developed further to find a usefor improved wastewater pollution control of high load wastewateremissions, such as those from the paper and pulp industry.

Declaration of competing interest

No conflict of interest exists as declared by the authors.

Acknowledgment

Author AKS thanks the to University Grant Commission (UGC) NewDelhi, for financial support, CSIR-Indian Institute of ToxicologyResearch, Lucknow, India, and Academy of Scientific & InnovativeResearch (AcSIR) (An Institute of National Importance)-Ghaziabad-201002, India are also thankfully acknowledged. Consejo Nacional deCiencia y Tecnología (MX) is thankfully acknowledged for partiallysupporting this work under Sistema Nacional de Investigadores (SNI)program awarded to Hafiz M.N. Iqbal (CVU: 735340). Author ARacknowledges Department of Biotechnology (DBT), Government ofIndia, New Delhi, for partially supporting of this work (Grant No. BT/PR20460/BCE/8/1386/2016. The contents of this manuscript hasrecieved manuscript allotment no (CSIR-IITR, manuscript communica-tion record) 3736.

References

Abhishek, A., Dwivedi, A., Tandan, N., Kumar, U., 2017. Comparative bacterial degradationand detoxification of model and Kraft lignin from pulp paperwastewater and its metab-olites. Appl. Water Sci. 7 (2), 757–767. https://doi.org/10.1007/s13201-015-0288-9.

Adeel, M., Song, X., Wang, Y., Francis, D., Yang, Y.J.E.I., 2017. Environmental impact of es-trogens on human, animal and plant life: a critical review. Environ. Int. 99, 107–119.https://doi.org/10.1016/j.envint.2016.12.010.

Adetutu, E.M., Gundry, T.D., Patil, S.S., Golneshin, A., Adigun, J., Bhaskarla, V., Aleer, S.,Shahsavari, E., Ross, E., Ball, A.S., 2015. Exploiting the intrinsic microbial degra-dative potential for field-based in situ dechlorination of trichloroethene contam-inated groundwater. J. Hazard. Mater. 300, 48–57. https://doi.org/10.1016/j.jhazmat.2015.06.055.

Akhtar, S., Husain, Q., 2006. Potential applications of immobilized bitter gourd (Momordicacharantia) peroxidase in the removal of phenols from polluted water. Chemosphere65 (7), 1228–1235. https://doi.org/10.1016/j.chemosphere.2006.04.049.

Alekhina, M., Ershova, O., Ebert, A., Heikkinen, S., Sixta, H., 2015. Softwood kraft lignin forvalue-added applications: fractionation and structural characterization. Ind. CropsProd. 66, 220–228. https://doi.org/10.1016/j.indcrop.2014.12.021.

Ali, H., Khan, E., Sajad, M.A.J.C., 2013. Phytoremediation of heavy metals-conceptsand applications. Chemosphere 91 (7), 869–881. https://doi.org/10.1016/j.chemosphere.2013.01.075.

Ali, S.S., Al-Tohamy, R., Koutra, E., El-Naggar, A.H., Kornaros, M., Sun, J., 2021. Valorizinglignin-like dyes and textile dyeing wastewater by a newly constructed lipid-producing and lignin modifying oleaginous yeast consortium valued for biodieseland bioremediation. J. Hazard. Mater. 403, 123575. https://doi.org/10.1016/j.jhazmat.2020.123575.

Arts, J., Kellert, M., Pottenger, L., Theuns-van Vliet, J., 2019. Evaluation of developmentaltoxicity of methyl chloride (chloromethane) in rats, mice, and rabbits. Regul. Toxicol.Pharmacol. 103, 274–281. https://doi.org/10.1016/j.yrtph.2019.02.001.

Ashraf, H., Husain, Q.J.D., 2010. Studies on bitter gourd peroxidase catalyzed removal of p-bromophenol from wastewater. Desalination 262 (1–3), 267–272. https://doi.org/10.1016/j.desal.2010.05.044.

Ashrafi, O., Yerushalmi, L., Haghighat, F., 2015. Wastewater treatment in the pulp-and-paper industry: a review of treatment processes and the associated green-house gas emission. J. Environ. Manag. 158, 146–157. https://doi.org/10.1016/j.jenvman.2015.05.010.

Aukema, K.G., Escalante, D.E., Maltby, M.M., Bera, A.K., Aksan, A., Wackett, L.P.J.E., 2017. Insilico identification of bioremediation potential: carbamazepine and other recalci-trant personal care products. Environ. Sci. Technol. 51 (2), 880–888. https://doi.org/10.1021/acs.est.6b04345.

Awasthi, M., Jaiswal, N., Singh, S., Pandey, V.P., Dwivedi, U.N., 2015. Moleculardocking and dynamics simulation analyses unraveling the differential enzymaticcatalysis by plant and fungal laccases with respect to lignin biosynthesis anddegradation. J. Biomol. Struct. Dynam. 33 (9), 1835–1849. https://doi.org/10.1080/07391102.2014.975282.

16

Azad, M.A.K., Amin, L., Sidik, N.M., 2014. Genetically engineered organisms for bioremedi-ation of pollutants in contaminated sites. Chin. Sci. Bull. 59 (8), 703–714. https://doi.org/10.1007/s11434-013-0058-8.

Azubuike, C.C., Chikere, C.B., Okpokwasili, G.C., 2016. Bioremediation techniques-classification based on site of application: principles, advantages, limitations andprospects. World J. Microbiol. Biotechnol. 32 (11), 180. https://doi.org/10.1007/s11274-016-2137-x.

Baghel, S., Anandkumar, J., 2019. Biodepolymerization of Kraft lignin for production andoptimization of vanillin using mixed bacterial culture. Bioresour. Technol. Rep. 8,100335. https://doi.org/10.1016/j.biteb.2019.100335.

Baghel, S., Sahariah, B.P., Anandkumar, J., 2020. Bioremediation of lignin-rich pulp andpaper industry effluent. In: Shah, M., Banerjee, A. (Eds.), Combined Application ofPhysico-chemical & Microbiological Processes for Industrial Effluent TreatmentPlant. Springer Singapore, Singapore, pp. 261–278 https://doi.org/10.1007/978-981-15-0497-6_12.

Bajpai, P., 2018. Chapter 12— Pulping fundamentals. In: Bajpai, P. (Ed.), Biermann’s Hand-book of Pulp and Paper, Third edition Elsevier, pp. 295–351 https://doi.org/10.1016/B978-0-12-814240-0.00012-4.

Barber, E.A., Liu, Z., Smith, S.R., 2020. Organic contaminant biodegradation by oxidoreduc-tase enzymes in wastewater treatment. Microorganisms 8 (1), 122. https://doi.org/10.3390/microorganisms8010122.

Baric, M., Pierro, L., Pietrangeli, B., Papini, M.P.J.N.B., 2014. Polyhydroxyalkanoate (PHB) asa slow-release electron donor for advanced in situ bioremediation of chlorinatedsolvent-contaminated aquifers. New Biotechnol. 31 (4), 377–382. https://doi.org/10.1016/j.nbt.2013.10.008.

Basharat, Z., Novo, L.A.B., Yasmin, A., 2018. Genome editing weds CRISPR: what is in it forphytoremediation? Plants 7 (3), 51. https://doi.org/10.3390/plants7030051.

Beans, C., 2017. Core concept: phytoremediation advances in the lab but lags in the field.Proc. Nat. Acad. Sci. 114 (29), 7475. https://doi.org/10.1073/pnas.1707883114.

Becker, J., Wittmann, C., 2019. A field of dreams: lignin valorization into chemicals, mate-rials, fuels, and health-care products. Biotechnol. Adv. 37 (6), 107360. https://doi.org/10.1016/j.biotechadv.2019.02.016.

Behler, J., Vijay, D., Hess, W.R., Akhtar, M.K., 2018. CRISPR-based technologies for meta-bolic engineering in Cyanobacteria. Trend. Biotechnol. 36 (10), 996–1010. https://doi.org/10.1016/j.tibtech.2018.05.011.

Benjamin, S.R., de Lima, F., Rathoure, A.K., 2019. Genetically engineered microorganismsfor bioremediation processes: GEMs for bioremediaton. Biotechnology: Concepts,Methodologies, Tools, and Applications. IGI Global, pp. 1607–1634 https://doi.org/10.4018/978-1-5225-8903-7.ch067.

Bilal, M., Iqbal, H.M.N., 2020. Microbial peroxidases and their unique catalytic potentiali-ties to degrade environmentally related pollutants. In: Arora, P.K. (Ed.), MicrobialTechnology for Health and Environment. Springer Singapore, Singapore, pp. 1–24https://doi.org/10.1007/978-981-15-2679-4_1.

Bilal, M., Adeel, M., Rasheed, T., Zhao, Y., Iqbal, H.M.N., 2019. Emerging contaminants ofhigh concern and their enzyme-assisted biodegradation — a review. Environ. Int.124, 336–353. https://doi.org/10.1016/j.envint.2019.01.011.

Blánquez, A., Rodríguez, J., Brissos, V., Mendes, S., Martins, L.O., Ball, A.S., Arias, M.E.,Hernández, M., 2019. Decolorization and detoxification of textile dyes using a versa-tile Streptomyces laccase-natural mediator system. Saudi J. Biol. Sci. 26 (5), 913–920.https://doi.org/10.1016/j.sjbs.2018.05.020.

Bortesi, L., Fischer, R., 2015. The CRISPR/Cas9 system for plant genome editing andbeyond. Biotechnol. Adv. 33 (1), 41–52. https://doi.org/10.1016/j.biotechadv.2014.12.006.

Bosque, I., Magallanes, G., Rigoulet, M., Kärkäs, M.D., Stephenson, C.R.J.A., 2017. Redox ca-talysis facilitates lignin depolymerization. ACS Cent. Sci. 3 (6), 621–628. https://doi.org/10.1021/acscentsci.7b00140.

Brissos, V., Tavares, D., Sousa, A.C., Robalo, M.P., Martins, L.O., 2017. Engineering a bacte-rial DyP-type peroxidase for enhanced oxidation of lignin-related phenolics at alka-line pH. ACS Catal. 7 (5), 3454–3465. https://doi.org/10.1021/acscatal.6b03331.

Calafat, A.M., Ye, X., Wong, L.-Y., Reidy, J.A., Needham, L.L., 2008. Exposure of the US pop-ulation to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ. HealthPerspect. 116 (1), 39–44. https://doi.org/10.1289/ehp.10753.

Carbajo, J., Bahamonde, A., Faraldos, M., 2017. Photocatalyst performance in wastewatertreatment applications: towards the role of TiO2 properties. Mol. Catal. 434,167–174. https://doi.org/10.1016/j.mcat.2017.03.018.

Cavinato, C., Ugurlu, A., de Godos, I., Kendir, E., Gonzalez-Fernandez, C., 2017. 7 — Biogasproduction from microalgae. In: Gonzalez-Fernandez, C., Muñoz, R. (Eds.),Microalgae-based Biofuels and Bioproducts. Woodhead Publishing, pp. 155–182https://doi.org/10.1016/B978-0-08-101023-5.00007-8.

Chagas, P.M.B., Torres, J.A., Silva, M.C., Corrêa, A.D., 2015. Immobilized soybean hull perox-idase for the oxidation of phenolic compounds in coffee processing wastewater. Int.J. Biol. Macromol. 81, 568–575. https://doi.org/10.1016/j.ijbiomac.2015.08.061.

Chandra, R., Sharma, P., Yadav, S., Tripathi, S., 2018. Biodegradation of endocrine-disrupting chemical and residual organic pollutants of pulp and paper mill efflu-ent by biostimulation. Front. Microbiol. 9, 960. https://doi.org/10.3389/fmicb.2018.00960.

Chauhan, P.S., 2020. Role of various bacterial enzymes in complete depolymerization oflignin: a review. Biocatal. Agric. Biotechnol. 23, 101498. https://doi.org/10.1016/j.bcab.2020.101498.

Chen, M., Zeng, G., Tan, Z., Jiang, M., Li, H., Liu, L., Zhu, Y., Yu, Z., Wei, Z., Liu, Y., Xie, G., 2011.Understanding lignin-degrading reactions of ligninolytic enzymes: binding affinityand interactional profile. PLoS One 6 (9), e25647. https://doi.org/10.1371/journal.pone.0025647.

Chen, Y.H., Chai, L.Y., Zhu, Y.H., Yang, Z.H., Zheng, Y., Zhang, H., 2012. Biodegradation ofKraft lignin by a bacterial strain Comamonas sp. B-9 isolated from eroded bamboo

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

slips. J. Appl. Microbiol. 112 (5), 900–906. https://doi.org/10.1111/j.1365-2672.2012.05275.x.

Cheng, P., Zhang, Q., Shan, X., Shen, D., Wang, B., Tang, Z., Jin, Y., Zhang, C., Huang, F., 2015.Cancer risks and long-term community-level exposure to pentachlorophenol in con-taminated areas, China. Environ. Sci. Pollut. Res. 22, 1309–1317. https://doi.org/10.1007/s11356-014-3469-4.

Cherian, S., Oliveira, M.M., 2005. Transgenic plants in phytoremediation: recent advancesand new possibilities. Environ. Sci. Technol. 39 (24), 9377–9390. https://doi.org/10.1021/es051134l.

Chikere, C.B., Chikere, B.O., Okpokwasili, G.C., 2012. Bioreactor-based bioremediation ofhydrocarbon-polluted Niger Delta marine sediment, Nigeria. 3 Biotech. 2 (1),53–66. https://doi.org/10.1007/s13205-011-0030-8.

Choudhary, A.K., Kumar, S., Sharma, C., 2015. Removal of chloro-organics and color frompulp and paper mill wastewater by polyaluminium chloride as coagulant. Desalin.Water Treat. 53 (3), 697–708. https://doi.org/10.1080/19443994.2013.848670.

Chung, H., Washburn, N.R., 2016. 2— Extraction and types of lignin. In: Faruk, O., Sain, M.(Eds.), Lignin in Polymer Composites. William Andrew Publishing, pp. 13–25 https://doi.org/10.1016/B978-0-323-35565-0.00002-3.

Colpa, D., Fraaije, M., Bloois, E., 2014. DyP-type peroxidases: a promising and versatileclass of enzymes. J. Ind. Microbiol. Biotechnol. 41, 1–7. https://doi.org/10.1007/s10295-013-1371-6.

Cooke, P.S., Simon, L., Denslow, N.D., 2013. Endocrine disruptors. Haschek andRousseaux's Handbook of Toxicologic Pathology. Elsevier, pp. 1123–1154 https://doi.org/10.1016/B978-0-12-415759-0.00037-6.

Deeba, F., Pruthi, V., Negi, Y.S., 2018. Effect of emerging contaminants from paper mill in-dustry into the environment and their control. In: Gupta, T., Agarwal, A.K., Agarwal,R.A., Labhsetwar, N.K. (Eds.), Environmental Contaminants: Measurement, Modellingand Control. Springer Singapore, Singapore, pp. 391–408 https://doi.org/10.1007/978-981-10-7332-8_17.

Dey, S., Choudhury, M.D., Das, S.J.F., Life, A., 2018. Assessment of pulp and paper mill efflu-ent quality and its toxicity to fingerlings of Cyprinus carpio. Fish. Aquat. Life 26 (4),243–256. https://doi.org/10.2478/aopf-2018-0028.

Donohoue, P.D., Barrangou, R., May, A.P., 2018. Advances in industrial biotechnology usingCRISPR-Cas systems. Trend. Biotechnol. 36 (2), 134–146. https://doi.org/10.1016/j.tibtech.2017.07.007.

Du, X., Li, J., Lindström, M.E., 2014. Modification of industrial softwood kraft lignin usingMannich reaction with and without phenolation pretreatment. Ind. Crop. Prod. 52,729–735. https://doi.org/10.1016/j.indcrop.2013.11.035.

Dvořák, P., Nikel, P.I., Damborský, J., de Lorenzo, V., 2017. Bioremediation 3.0: engineeringpollutant-removing bacteria in the times of systemic biology. Biotechnol. Adv. 35 (7),845–866. https://doi.org/10.1016/j.biotechadv.2017.08.001.

Eapen, S., Singh, S., D'souza, S.J.B.A., 2007. Advances in development of transgenic plantsfor remediation of xenobiotic pollutants. Biotechnol. Adv. 25 (5), 442–451. https://doi.org/10.1016/j.biotechadv.2007.05.001.

Elisashvili, V., Kachlishvili, E., Asatiani, M.D., 2018. Efficient production of lignin-modifying enzymes and phenolics removal in submerged fermentation of olive millby-products by white-rot basidiomycetes. Int. Biodeterior. Biodegrad. 134, 39–47.https://doi.org/10.1016/j.ibiod.2018.08.003.

Falade, A.O., Eyisi, O.A.L., Mabinya, L.V., Nwodo, U.U., Okoh, A.I., 2017. Peroxidaseproduction and ligninolytic potentials of freshwater bacteria Raoultellaornithinolytica and Ensifer adhaerens. Biotechnol. Rep. 16, 12–17. https://doi.org/10.1016/j.btre.2017.10.001.

Falade, A.O., Mabinya, L.V., Okoh, A.I., Nwodo, U.U., 2018. Ligninolytic enzymes: versatilebiocatalysts for the elimination of endocrine-disrupting chemicals in wastewater.Microbiol. Open 7 (6), e00722. https://doi.org/10.1002/mbo3.722.

Flourat, A.L., Peru, A.A.M., Haudrechy, A., Renault, J.-H., Allais, F., 2019. First total synthesisof (β-5)-(β-O-4) dihydroxytrimer and dihydrotrimer of coniferyl alcohol (G): ad-vanced lignin model compounds. Front. Chem. 7, 842. https://doi.org/10.3389/fchem.2019.00842.

Fortunati, E., Luzi, F., Puglia, D., Torre, L., 2016. Chapter 1 — Extraction of lignocellulosicmaterials from waste products. In: Puglia, D., Fortunati, E., Kenny, J.M. (Eds.), Multi-functional Polymeric Nanocomposites Based on Cellulosic Reinforcements. WilliamAndrew Publishing, pp. 1–38 https://doi.org/10.1016/B978-0-323-44248-0.00001-8.

Foszpańczyk, M., Drozdek, E., Gmurek, M., Ledakowicz, S., 2018. Toxicity of aqueous mix-ture of phenol and chlorophenols upon photosensitized oxidation initiated by sun-light or vis-lamp. Environ. Sci. Pollut. Res. 25 (35), 34968–34975. https://doi.org/10.1007/s11356-018-1286-x.

Gadupudi, C.K., Rice, L., Xiao, L., Kantamaneni, K., 2019. Endocrine disrupting compoundsremoval methods from wastewater in the United Kingdom: a review. Science 1 (1),15. https://doi.org/10.3390/sci1010015.v1.

Garba, Z.N., Zhou, W., Lawan, I., Xiao, W., Zhang, M., Wang, L., Chen, L., Yuan, Z.J., 2019. Anoverview of chlorophenols as contaminants and their removal from wastewater byadsorption: a review. J. Environ. Manag. 241, 59–75. https://doi.org/10.1016/j.jenvman.2019.04.004.

Garg, S.K., Tripathi, M., 2011. Strategies for decolorization and detoxification of pulp andpaper mill effluent. Rev. Environ. Contam. Toxicol. 212, 113–136. https://doi.org/10.1007/978-1-4419-8453-1_4.

Gauchotte-Lindsay, C., Aspray, T.J., Knapp,M., Ijaz, U.Z., 2019. Systems biology approach toelucidation of contaminant biodegradation in complex samples — integration ofhigh-resolution analytical and molecular tools. Faraday Discuss. 218(0), 481–504.doi:https://doi.org/10.1039/C9FD00020H.

Gaur, N., Narasimhulu, K., Pydi Setty, Y., 2018. Extraction of ligninolytic enzymes fromnovel Klebsiella pneumoniae strains and its application in wastewater treatment.Appl. Water Sci. 8 (4), 111. https://doi.org/10.1007/s13201-018-0758-y.

Gelbke, H., Kayser, M., Poole, A., 2004. OECD test strategies and methods for endocrinedisruptors. Toxicology 205 (1–2), 17–25. https://doi.org/10.1016/j.tox.2004.06.034.

17

Ghattas, A.-K., Fischer, F., Wick, A., Ternes, T.A., 2017. Anaerobic biodegradation of(emerging) organic contaminants in the aquatic environment. Water Res. 116,268–295. https://doi.org/10.1016/j.watres.2017.02.001.

Gillet, S., Aguedo, M., Petitjean, L., Morais, A.R.C., da Costa Lopes, A.M., Łukasik, R.M.,Anastas, P.T., 2017. Lignin transformations for high value applications: towardstargeted modifications using green chemistry. Green Chem. 19 (18), 4200–4233.https://doi.org/10.1039/C7GC01479A.

González, P.S., Agostini, E., Milrad, S.R., 2008. Comparison of the removal of 2,4-dichloro-phenol and phenol from polluted water, by peroxidases from tomato hairy roots, andprotective effect of polyethylene glycol. Chemosphere 70 (6), 982–989. https://doi.org/10.1016/j.chemosphere.2007.08.025.

González-Riopedre, G., Fernández-García, M.I., Gómez-Fórneas, E., Maneiro, M., 2013. Bio-mimetic catalysts for oxidation of veratryl alcohol, a lignin model compound. Cata-lysts 3 (1), 232–246. https://doi.org/10.3390/catal3010232.

de Gonzalo, G., Colpa, D.I., Habib, M.H.M., Fraaije, M.W., 2016. Bacterial enzymes involvedin lignin degradation. J. Biotechnol. 236, 110–119. https://doi.org/10.1016/j.jbiotec.2016.08.011.

Granja-Travez, R.S., Persinoti, G.F., Squina, F.M., Bugg, T.D.H., 2020. Functional genomicanalysis of bacterial lignin degraders: diversity in mechanisms of lignin oxidationand metabolism. Appl. Microbiol. Biotechnol. 104 (8), 3305–3320. https://doi.org/10.1007/s00253-019-10318-y.

Grelska, A., Noszczyńska, M., 2020. White rot fungi can be a promising tool for removal ofbisphenol A, bisphenol S, and nonylphenol from wastewater. Environ. Sci. Poll. Res.27 (32), 39958–39976. https://doi.org/10.1007/s11356-020-10382-2.

Guadix-Montero, S., Sankar, M., 2018. Review on catalytic cleavage of C-C inter-unit link-ages in lignin model compounds: towards lignin depolymerisation. Topic. Catal. 61(3), 183–198. https://doi.org/10.1007/s11244-018-0909-2.

Hakala, T.K., Hildén, K., Maijala, P., Olsson, C., Hatakka, A., 2006. Differential regulation ofmanganese peroxidases and characterization of two variable MnP encoding genes inthe white-rot fungus Physisporinus rivulosus. Appl. Microbiol. Biotechnol. 73 (4),839–849. https://doi.org/10.1007/s00253-006-0541-0.

Haq, I., Kumar, S., Kumari, V., Singh, S.K., Raj, A., 2016. Evaluation of bioremediationpotentiality of ligninolytic Serratia liquefaciens for detoxification of pulp andpaper mill effluent. J. Hazard. Mater. 305, 190–199. https://doi.org/10.1016/j.jhazmat.2015.11.046.

Haq, I., Kumar, S., Raj, A., Lohani, M., Satyanarayana, G.N.V., 2017. Genotoxicity as-sessment of pulp and paper mill effluent before and after bacterial degradationusing Allium cepa test. Chemosphere 169, 642–650. https://doi.org/10.1016/j.chemosphere.2016.11.101.

Harayama, S., 1997. Polycyclic aromatic hydrocarbon bioremediation design. Curr. Opin.Biotechnol. 8 (3), 268–273. https://doi.org/10.1016/S0958-1669(97)80002-X.

Harman-Ware, A.E., Happs, R.M., Davison, B.H., Davis, M.F., 2017. The effect of coumarylalcohol incorporation on the structure and composition of lignin dehydrogenationpolymers. Biotechnol. Biofuels 10 (1), 281. https://doi.org/10.1186/s13068-017-0962-2.

Ház, A., Jablonský, M., Šurina, I., Kačík, F., Bubeníková, T., Ďurkovič, J.J.F., 2019. Chemicalcomposition and thermal behavior of Kraft lignins. Forests 10 (6), 483. https://doi.org/10.3390/f10060483.

He, W., Gao, W., Fatehi, P., 2017. Oxidation of Kraft lignin with hydrogen peroxide and itsapplication as a dispersant for kaolin suspensions. ACS Sust. Chem. Eng. 5 (11),10597–10605. https://doi.org/10.1021/acssuschemeng.7b02582.

Hintz, H.L., 2001. Paper: pulping and bleaching. In: Buschow, K.H.J., Cahn, R.W., Flemings,M.C., Ilschner, B., Kramer, E.J., Mahajan, S., Veyssière, P. (Eds.), Encyclopedia of Mate-rials: Science and Technology. Elsevier, Oxford, pp. 6707–6711 https://doi.org/10.1016/B0-08-043152-6/01187-6.

Hlihor, R.M., Gavrilescu, M., Tavares, T., Favier, L., Olivieri, G., 2017. Bioremediation: anoverview on current practices, advances, and new perspectives in environmental pol-lution treatment. Biomed. Res. Int. 2017, 6327610. https://doi.org/10.1155/2017/6327610.

Hong, C.Y., Park, S.Y., Kim, S.H., Lee, S.Y., Choi, W.S., Choi, I.G., 2016. Degradation and po-lymerization of monolignols by Abortiporus biennis, and induction of its degradationwith a reducing agent. J. Microbiol. 54 (10), 675–685. https://doi.org/10.1007/s12275-016-6158-9.

Hooda, R., Bhardwaj, N.K., Singh, P., 2015. Screening and identification of ligninolytic bac-teria for the treatment of pulp and paper mill effluent. Water Air Soil Pollut. 226 (9),305. https://doi.org/10.1007/s11270-015-2535-y.

Huang, W., He, Y., Xiao, J., Huang, Y., Li, A., He, M., Wu, K., 2019. Risk of breast cancer andadipose tissue concentrations of polychlorinated biphenyls and organochlorine pesti-cides: a hospital-based case-control study in Chinese women. Environ. Sci. Pollut. Res.26 (31), 32128–32136. https://doi.org/10.1007/s11356-019-06404-3.

Hubbe, M., Metts, J., Hermosilla, D., Blanco, A., Yerushalmi, L., Haghighat, F., Lindholm-Lehto, P., Khodaparast, Z., Kamali, M., Elliott, A., 2016.Wastewater treatment and rec-lamation: a review of pulp and paper industry practices and opportunities.Bioresources 11, 7953–8091. https://doi.org/10.15376/biores.11.3.Hubbe.

Iorhemen, O.T., Hamza, R.A., Tay, J.H., 2016. Membrane bioreactor (MBR) technology forwastewater treatment and reclamation: membrane fouling. Membranes 6 (2), 33.https://doi.org/10.3390/membranes6020033.

Jaiswal, S., Singh, D.K., Shukla, P., 2019. Gene editing and systems biology tools for pesti-cide bioremediation: a review. Front. Microbiol. 10, 87. https://doi.org/10.3389/fmicb.2019.00087.

Jambor, T., Greifova, H., Bistakova, J., Lukac, N.J.E.D., 2018. Endocrine Disruptors and Re-productive Health in Males. , p. 99 https://doi.org/10.5772/intechopen.78538.

James, C.A., Strand, S.E., 2009. Phytoremediation of small organic contaminants usingtransgenic plants. Curr. Opin. Biotechnol. 20 (2), 237–241. https://doi.org/10.1016/j.copbio.2009.02.014.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

Jan, J., Vrbic, V., 2000. Polychlorinated biphenyls cause developmental enamel defects inchildren. Caries Res. 34 (6), 469–473. https://doi.org/10.1159/000016625.

Jan, J., Sovcikova, E., Kocan, A., Wsolova, L., Trnovec, T., 2007. Developmental dental de-fects in children exposed to PCBs in eastern Slovakia. Chemosphere 67 (9),S350–S354. https://doi.org/10.1016/j.chemosphere.2006.05.148.

Janssen, D.B., Stucki, G., 2020. Perspectives of genetically engineeredmicrobes for ground-water bioremediation. Environ. Sci. Process. Impact. 22 (3), 487–499. https://doi.org/10.1039/C9EM00601J.

Janusz, G., Pawlik, A., Sulej, J., Świderska-Burek, U., Jarosz-Wilkołazka, A., Paszczyński, A.,2017. Lignin degradation: microorganisms, enzymes involved, genomes analysis andevolution. FEMS Microbiol. Rev. 41 (6), 941–962. https://doi.org/10.1093/femsre/fux049.

Jariyal, M., Yadav, M., Singh, N.K., Yadav, S., Sharma, I., Dahiya, S., Thanki, A., 2020. Micro-bial remediation progress and future prospects. Bioremediation of Pollutants.Elsevier, pp. 187–214 https://doi.org/10.1016/B978-0-12-819025-8.00008-9.

Jayaraj, R., Megha, P., Sreedev, P., 2016. Organochlorine pesticides, their toxic effects onliving organisms and their fate in the environment. Interdiscip. Toxicol. 9 (3–4),90–100. https://doi.org/10.1515/intox-2016-0012.

Jeon, C.O., Madsen, E.L., 2013. In situ microbial metabolism of aromatic-hydrocarbon en-vironmental pollutants. Curr. Opin. Biotechnol. 24 (3), 474–481. https://doi.org/10.1016/j.copbio.2012.09.001.

Jesitha, K., Harikumar, P.S., 2018. Development of a bioreactor system for the remediationof endosulphan. H2Open J. 2 (1), 1–8. https://doi.org/10.2166/h2oj.2019.018.

Joffe, M., 2003. Infertility and environmental pollutants. Brit. Med. Bull. 68 (1), 47–70.https://doi.org/10.1093/bmb/ldg025.

Julkapli, N.M., Bagheri, S., 2016. Developments in nano-additives for paper industry.J. Wood Sci. 62, 117–130. https://doi.org/10.1007/s10086-015-1532-5.

Kallio, J.P., Gasparetti, C., Andberg, M., Boer, H., Koivula, A., Kruus, K., Rouvinen, J.,Hakulinen, N., 2011. Crystal structure of an ascomycete fungal laccase from Thielaviaarenaria-common structural features of asco-laccases. FEBS J. 278 (13), 2283–2295.https://doi.org/10.1111/j.1742-4658.2011.08146.x.

Kalyani, D.C., Munk, L., Mikkelsen, J.D., Meyer, A.S., 2016. Molecular and biochemical char-acterization of a new thermostable bacterial laccase from Meiothermus ruber DSM1279. RSC Adv. 6 (5), 3910–3918. https://doi.org/10.1039/C5RA24374B.

Kamimura, N., Sakamoto, S., Mitsuda, N., Masai, E., Kajita, S., 2019. Advances in microbiallignin degradation and its applications. Curr. Opin. Biotechnol. 56, 179–186. https://doi.org/10.1016/j.copbio.2018.11.011.

Kang, J.W., 2014. Removing environmental organic pollutants with bioremediation andphytoremediation. Biotechnol. Lett. 36, 1129–1139. https://doi.org/10.1007/s10529-014-1466-9.

Karigar, C.S., Rao, S.S., 2011. Role of microbial enzymes in the bioremediation of pollut-ants: a review. Enz. Res. 2011, 805187. https://doi.org/10.4061/2011/805187.

Karp, P.D., Latendresse, M., Caspi, R., 2011. The pathway tools pathway prediction algo-rithm. Stand. Genomic Sci. 5 (3), 424–429. https://doi.org/10.4056/sigs.1794338.

Kasahara, E., Sato, E.F., Miyoshi, M., Konaka, R., Hiramoto, K., Sasaki, J., Tokuda, M., Nakano,Y., Inoue, M.J.B.J., 2002. Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl) phthalate. Biochem. J. 365 (3), 849–856. https://doi.org/10.1042/bj20020254.

Kaur, D., Bhardwaj, N.K., Lohchab, R.K., 2019. Impact of modifying conventional chlorinedioxide stage to hot chlorine dioxide during rice straw pulp bleaching on pulp,paper and effluent characteristics. Cellulose 26 (12), 7469–7482. https://doi.org/10.1007/s10570-019-02616-5.

Kawamoto, H., 2017. Lignin pyrolysis reactions. J. Wood Sci. 63 (2), 117–132. https://doi.org/10.1007/s10086-016-1606-z.

Khorsandi, H., Ghochlavi, N., Aghapour, A.A., 2018. Biological degradation of 2,4,6-trichlorophenol by a sequencing batch reactor. Environ. Proc. 5 (4), 907–917.https://doi.org/10.1007/s40710-018-0333-4.

Kim, E.Y., Choi, Y.J., Chae, H.J., Chu, K.H., 2006. Removal of aqueous pentachlorophenol byhorseradish peroxidase in the presence of surfactants. Biotechnol. Bioprocess Eng. 11(5), 462–465. https://doi.org/10.1007/BF02932315.

Kim, H., Ralph, J., 2005. Simplified preparation of coniferyl and sinapyl alcohols. J. Agric.Food Chem. 53 (9), 3693–3695. https://doi.org/10.1021/jf047787n.

Kirby, R., 2005. Actinomycetes and lignin degradation. In: Laskin, A.I., Bennett, J.W., Gadd,G.M., Sariaslani, S. (Eds.), Advances in Applied Microbiology. Academic Press,pp. 125–168 https://doi.org/10.1016/S0065-2164(05)58004-3.

Kirk, T.K., Farrell, R.L., 1987. Enzymatic “combustion”: the microbial degradation oflignin. Ann. Rev. Microbiol. 41, 465–505. https://doi.org/10.1146/annurev.mi.41.100187.002341.

Kleinman, M.H., Baertschi, S.W., Alsante, K.M., Reid, D.L., Mowery, M.D., Shimanovich, R.,Foti, C., Smith, W.K., Reynolds, D.W., Nefliu, M., Ott, M.A., 2014. In silico predictionof pharmaceutical degradation pathways: a benchmarking study. Mol. Pharm. 11(11), 4179–4188. https://doi.org/10.1021/mp5003976.

Kumar, A., Singh, A.K., Chandra, R., 2020a. Comparative analysis of residual organic pollut-ants from bleached and unbleached paper mill wastewater and their toxicity onPhaseolus aureus and Tubifex tubifex. Urban Water J. https://doi.org/10.1080/1573062X.2020.1836238 (on-line Oct. 23. 2020).

Kumar, R.S., Singh, D., Bose, S.K., Trivedi, P.K., 2020b. 7— Biodegradation of environmentalpollutant through pathways engineering and genetically modified organisms ap-proaches. In: Chowdhary, P., Raj, A., Verma, D., Akhter, Y. (Eds.), Microorganismsfor Sustainable Environment and Health. Elsevier, pp. 137–165 https://doi.org/10.1016/B978-0-12-819001-2.00007-3.

Kumar, S., Dagar, V.K., Khasa, Y.P., Kuhad, R.C., 2013. Genetically modifiedmicroorganisms(GMOs) for bioremediation. In: Kuhad, R.C., Singh, A. (Eds.), Biotechnology for Envi-ronmental Management and Resource Recovery. Springer India, India, pp. 191–218https://doi.org/10.1007/978-81-322-0876-1_11.

18

Kumar, V., Chopra, A.K., 2016. Reduction of pollution load of paper mill effluent byphytoremediation technique using water caltrop (Trapa natans L.). Cogent Environ.Sci. 2 (1), 1153216. https://doi.org/10.1080/23311843.2016.1153216.

Kumar, V., Singh, J., Kumar, P., 2020c. Regression models for removal of heavy metals bywater hyacinth (Eichhornia crassipes) from wastewater of pulp and paper processingindustry. Environ. Sust. 3 (1), 35–44. https://doi.org/10.1007/s42398-019-00093-x.

Kurnik, K., Treder, K., Skorupa-Kłaput, M., Tretyn, A., Tyburski, J., 2015. Removal of phenolfrom synthetic and industrial wastewater by potato pulp peroxidases. Water Air SoilPollut. 226 (8), 254. https://doi.org/10.1007/s11270-015-2517-0.

Kurnik, K., Treder, K., Twarużek, M., Grajewski, J., Tretyn, A., Tyburski, J., 2018. Potato pulpas the peroxidase source for 2,4-dichlorophenol removal. Waste Biomass Valor. 9 (6),1061–1071. https://doi.org/10.1007/s12649-017-9863-7.

Lee, J., Koh, D., Andijani, M., Saw, S.M., Munoz, C., Chia, S.E., Wong, M.L., Hong, C.Y., Ong,C.N., 2002. Effluents from a pulp and paper mill: a skin and health survey of childrenliving in upstream and downstream villages. Occup. Environ. Med. 59 (6), 373.https://doi.org/10.1136/oem.59.6.373.

Leigh, M.B., Prouzová, P., Macková, M., Macek, T., Nagle, D.P., Fletcher, J.S., 2006.Polychlorinated biphenyl (PCB)-degrading bacteria associated with trees in a PCB-contaminated site. Appl. Environ. Microbiol. 72 (4), 2331–2342. https://doi.org/10.1128/AEM.72.4.2331-2342.2006.

Lendvay, J., Löffler, F.E., Dollhopf, M., Aiello, M., Daniels, G., Fathepure, B., Gebhard, M.,Heine, R., Helton, R., 2003. Bioreactive barriers: a comparison of bioaugmentationand biostimulation for chlorinated solvent remediation. Environ. Sci. Technol. 37(7), 1422–1431. https://doi.org/10.1021/es025985u.

Liu, L., Bilal, M., Duan, X., Iqbal, H.M.N., 2019. Mitigation of environmental pollution by ge-netically engineered bacteria — current challenges and future perspectives. Sci. TotalEnviron. 667, 444–454. https://doi.org/10.1016/j.scitotenv.2019.02.390.

Liu, X., 2020. Microbial technology for the sustainable development of energy and envi-ronment. Biotechnol. Rep. 27, e00486. https://doi.org/10.1016/j.btre.2020.e00486.

Liu, Z., Liu, Y., Zeng, G., Shao, B., Chen, M., Li, Z., Jiang, Y., Liu, Y., Zhang, Y., Zhong, H., 2018.Application of molecular docking for the degradation of organic pollutants in the en-vironmental remediation: a review. Chemosphere 203, 139–150. https://doi.org/10.1016/j.chemosphere.2018.03.179.

Lobo, C.C., Bertola, N.C., Contreras, E.M., Zaritzky, N.E., 2018. Monitoring and modeling 4-chlorophenol biodegradation kinetics by phenol-acclimated activated sludge byusing open respirometry. Environ. Sci. Pollut. Res. 25 (22), 21272–21285. https://doi.org/10.1007/s11356-017-9735-5.

Lone, M.I., He, Z.-L., Stoffella, P.J., Yang, X.E., 2008. Phytoremediation of heavy metal pol-luted soils and water: progresses and perspectives. J Zhejiang Univ Sci B 9 (3),210–220. https://doi.org/10.1631/jzus.B0710633.

Lundell, T.K., Mäkelä, M.R., Hildén, K., 2010. Lignin-modifying enzymes in filamentous ba-sidiomycetes—ecological, functional and phylogenetic review. J. Basic Microbiol. 50(1), 5–20. https://doi.org/10.1002/jobm.200900338.

Macek, T., Kotrba, P., Svatos, A., Novakova, M., Demnerova, K., Mackova, M., 2008. Novelroles for genetically modified plants in environmental protection. Trend. Biotechnol.26 (3), 146–152. https://doi.org/10.1016/j.tibtech.2007.11.009.

Malhotra, R., Prakash, D., Shukla, S.K., Kim, T., Kumar, S., Rao, N.J., 2013. Comparative studyof toxic chlorophenolic compounds generated in various bleaching sequences ofwheat straw pulp. Clean Techn. Environ. Policy 15, 999–1011. https://doi.org/10.1007/s10098-013-0578-6.

Malla, M.A., Dubey, A., Yadav, S., Kumar, A., Hashem, A., Abd Allah, E.F., 2018. Understand-ing and designing the strategies for the microbe-mediated remediation of environ-mental contaminants using omics approaches. Front. Microbiol. 9, 1132. https://doi.org/10.3389/fmicb.2018.01132.

Mandeep, Gupta, G.K., Liu, H., Shukla, P., 2019. Pulp and paper industry-based pollutants,their health hazards and environmental risks. Curr. Opin. Environ. Sci. Health 12,48–56. https://doi.org/10.1016/j.coesh.2019.09.010.

Martínková, L., Kotik, M., Marková, E., Homolka, L., 2016. Biodegradation of phenolic com-pounds by Basidiomycota and its phenol oxidases: a review. Chemosphere 149,373–382. https://doi.org/10.1016/j.chemosphere.2016.01.022.

Mathew, A.K., Abraham, A., Mallapureddy, K.K., Sukumaran, R.K., 2018. Chapter 9— Ligno-cellulosic biorefinery wastes, or resources? In: Bhaskar, T., Pandey, A., Mohan, S.V.,Lee, D.-J., Khanal, S.K. (Eds.), Waste Biorefinery. Elsevier, pp. 267–297 https://doi.org/10.1016/B978-0-444-63992-9.00009-4

Mathews, S.L., Grunden, A.M., Pawlak, J., 2016. Degradation of lignocellulose and lignin byPaenibacillus glucanolyticus. Int. Biodeterior. Biodegrad. 110, 79–86. https://doi.org/10.1016/j.ibiod.2016.02.012.

Mehmood, K., Rehman, S.K., Wang, J., Farooq, F., Mahmood, Q., Jadoon, A.M., Javed, M.F.,Ahmad, I., 2019. Treatment of pulp and paper industrial effluent using physicochem-ical process for recycling. Water 11 (11), 2–15. https://doi.org/10.3390/w11112393.

Mehra, R., Meyer, A.S., Kepp, K., 2018a. Molecular dynamics derived life times of activesubstrate binding poses explain KM of laccase mutants. RSC Adv. 8, 36915–36926.https://doi.org/10.1039/c8ra07138a.

Mehra, R., Muschiol, J., Meyer, A.S., Kepp, K.P., 2018b. A structural-chemical explanation offungal laccase activity. Sci. Rep. 8, 17285. https://doi.org/10.1038/s41598-018-35633-8.

Mester, T., Ambert-Balay, K., Ciofi-Baffoni, S., Banci, L., Jones, A.D., Tien, M., 2001. Oxida-tion of a tetrameric nonphenolic lignin model compound by lignin peroxidase.J. Biol. Chem. 276 (25), 22985–22990. https://doi.org/10.1074/jbc.M010739200.

Miki, Y., Calviño, F.R., Pogni, R., Giansanti, S., Ruiz-Dueñas, F.J., Martínez, M.J., Basosi, R.,Romero, A., Martínez, A.T., 2011. Crystallographic, kinetic, and spectroscopic studyof the first ligninolytic peroxidase presenting a catalytic tyrosine. J. Biol. Chem. 286(17), 15525–15534. https://doi.org/10.1074/jbc.M111.220996.

Min, K., Gong, G., Woo, H.M., Kim, Y., Um, Y., 2015. A dye-decolorizing peroxidase fromBacillus subtilis exhibiting substrate-dependent optimum temperature for dyes andβ-ether lignin dimer. Sci. Rep. 5 (1), 8245. https://doi.org/10.1038/srep08245.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

Mishra, B., Varjani, S., Agrawal, D.C., Mandal, S.K., Ngo, H.H., Taherzadeh, M.J., Chang, J.-S.,You, S., Guo,W., 2020. Engineering biocatalyticmaterial for the remediation of pollut-ants: a comprehensive review. Environ. Technol. Innov. 20, 101063. https://doi.org/10.1016/j.eti.2020.101063.

Monge-Corella, S., García-Pérez, J., Aragonés, N., Pollán, M., Pérez-Gómez, B., López-Abente, G., 2008. Lung cancer mortality in towns near paper, pulp and board indus-tries in Spain: a point source pollution study. BMC Public Health 8, 288. https://doi.org/10.1186/1471-2458-8-288.

Moriya, Y., Shigemizu, D., Hattori, M., Tokimatsu, T., Kotera, M., Goto, S., Kanehisa, M.,2010. PathPred: an enzyme-catalyzed metabolic pathway prediction server. Nucl.Acid. Res. 38 (Web Server issue), W138–W143. https://doi.org/10.1093/nar/gkq318.

Mounteer, A., Souza, L., Silva, C., 2007. Potential for enhancement of aerobic biological re-moval of recalcitrant organic matter in bleached pulpmill effluents. Environ. Technol.28, 157–164. https://doi.org/10.1080/09593332808618775.

Mu, L., Wu, J., Matsakas, L., Chen, M., Vahidi, A., Grahn, M., Rova, U., Christakopoulos, P.,Zhu, J., Shi, Y., 2018. Lignin from hardwood and softwood biomass as a lubricating ad-ditive to ethylene glycol. Molecules 23 (3), 537. https://doi.org/10.3390/molecules23030537.

Munk, L., Sitarz, A., Kalyani, D., Mikkelsen, J.D., Meyer, A., 2015. Can laccases catalyze bondcleavage in lignin? Biotechnol. Adv. 33, 13–24. https://doi.org/10.1016/j.biotechadv.2014.12.008.

Nath, S., 2016. Effect of paper mill effluents on morphological and hematological indicesof Amblyceps mangois. J. Fish. Aquat. Sci. 11, 225–231. https://doi.org/10.3923/jfas.2016.225.231.

National Mission for Clean Ganga (NMCG), 2019. Strategy for improving condition ofwater bodies in the vicinity of pulp and paper industries in Ganga river basin.http://cganga.org/wp-content/uploads/sites/3/2019/06/PulpPaper_Ganga-Pollution-Assessment-Document_final-Single.pdf (accessed Nov. 10. 2020).

Nimrod, A.C., Benson, W.H., 1996. Environmental estrogenic effects of alkylphenolethoxylates. Crit. Rev. Toxicol. 26 (3), 335–364. https://doi.org/10.3109/10408449609012527.

Ohura, T., 2007. Environmental behavior, sources, and effects of chlorinated polycyclic ar-omatic hydrocarbons. Sci. World J. 7, 372–380. https://doi.org/10.1100/tsw.2007.75.

Ong, S.-T., Keng, P.-S., Lee, W.-N., Ha, S.-T., Hung, Y.-T., 2011. Dye waste treatment. Water3 (1), 157–176. https://doi.org/10.3390/w3010157.

Pandey, J., Chauhan, A., Jain, R.K., 2009. Integrative approaches for assessing the ecologicalsustainability of in situ bioremediation. FEMS Microbiol. Rev. 33 (2), 324–375.https://doi.org/10.1111/j.1574-6976.2008.00133.x.

Parenty, A.D., Button, W.G., Ott, M.A., 2013. An expert system to predict the forced degra-dation of organic molecules. Mol. Pharm. 10 (8), 2962–2974. https://doi.org/10.1021/mp400083h.

Pariselli, F., Sacco, M., Ponti, J., Rembges, D., 2009. Effects of toluene and benzene air mix-tures on human lung cells (A549). Exp. Toxicol. Pathol. 61 (4), 381–386. https://doi.org/10.1016/j.etp.2008.10.004.

Pathak, N., Tran, V.H., Phuntsho, S., Shon, H.Y., 2020. Chapter 10—Membrane bioreactorsfor the removal of micro-pollutants. In: Varjani, S., Pandey, A., Tyagi, R.D., Ngo, H.H.,Larroche, C. (Eds.), Current Developments in Biotechnology and Bioengineering.Elsevier, pp. 231–252 https://doi.org/10.1016/B978-0-12-819594-9.00010-3.

Paz, A., Costa-Trigo, I., Tugores, F., Míguez, M., de la Montaña, J., Domínguez, J.M., 2019.Biotransformation of phenolic compounds by Bacillus aryabhattai. Bioprocess Biosyst.Eng. 42 (10), 1671–1679. https://doi.org/10.1007/s00449-019-02163-0.

Paz, A., Costa-Trigo, I., Oliveira, R.P.d.S., Domínguez, J.M., 2020. Ligninolytic enzymes ofendospore-forming Bacillus aryabhattai BA03. Curr. Microbiol. 77 (5), 702–709.https://doi.org/10.1007/s00284-019-01856-9.

Perna, V., Agger, J.W., Holck, J., Meyer, A.S., 2018. Multiple reaction monitoring for quan-titative laccase kinetics by LC-MS. Sci. Rep. 8, 8114. https://doi.org/10.1038/s41598-018-26523-0.

Pieper, D.H., Reineke, W., 2000. Engineering bacteria for bioremediation. Curr. Opin.Biotechnol. 11 (3), 262–270. https://doi.org/10.1016/S0958-1669(00)00094-X.

Pilon-Smits, E.A.H., LeDuc, D.L., 2009. Phytoremediation of selenium using transgenicplants. Curr. Opin. Biotechnol. 20 (2), 207–212. https://doi.org/10.1016/j.copbio.2009.02.001.

Pino-Herrera, D.O., Pechaud, Y., Huguenot, D., Esposito, G., van Hullebusch, E.D., Oturan,M.A., 2017. Removal mechanisms in aerobic slurry bioreactors for remediation ofsoils and sediments polluted with hydrophobic organic compounds: an overview.J. Hazard. Mater. 339, 427–449. https://doi.org/10.1016/j.jhazmat.2017.06.013.

Poulopoulos, S.G., Yerkinova, A., Ulykbanova, G., Inglezakis, V.J., 2019. Photocatalytic treat-ment of organic pollutants in a synthetic wastewater using UV light and combina-tions of TiO2, H2O2 and Fe(III). PLoS One 14 (5), e0216745. https://doi.org/10.1371/journal.pone.0216745.

Pramanik, S., Chaudhuri, S., 2018. Laccase activity and azo dye decolorization poten-tial of Podoscypha elegans. Mycobiol. 46 (1), 79–83. https://doi.org/10.1080/12298093.2018.1454006.

Pu, Y., Hu, F., Huang, F., Ragauskas, A.J., 2015. Lignin structural alterations in thermochem-ical pretreatments with limited delignification. BioEner. Res. 8 (3), 992–1003. https://doi.org/10.1007/s12155-015-9655-5.

Qayyum, H., Maroof, H., Yasha, K., 2009. Remediation and treatment of organopollutantsmediated by peroxidases: a review. Crit. Rev. Biotechnol. 29 (2), 94–119. https://doi.org/10.1080/07388550802685306.

Qi-He, C., Krügener, S., Hirth, T., Rupp, S., Zibek, S., 2011. Co-cultured production of lignin-modifying enzymes with white-rot fungi. Appl. Biochem. Biotechnol. 165 (2),700–718. https://doi.org/10.1007/s12010-011-9289-9.

Qin, C., Huang, L., Lv, Q., Nie, S., Yao, S., 2019. Structural transformation of lignin from eu-calyptus during chlorine dioxide bleaching. Bioresources 14, 1265–1278. Doi:10.15376/biores.14.1.1265-1278.

19

Radotić, K., Micic, M., 2016. Methods for Extraction and Purification of Lignin and CelluloseFrom Plant Tissues. , pp. 365–376 https://doi.org/10.1007/978-1-4939-3185-9_26.

Rahmanpour, R., Rea, D., Jamshidi, S., Fülöp, V., Bugg, T.D., 2016. Structure ofThermobifida fusca DyP-type peroxidase and activity towards Kraft lignin and lig-nin model compounds. Arch. Biochem. Biophys. 594, 54–60. https://doi.org/10.1016/j.abb.2016.02.019.

Raies, A.B., Bajic, V.B., 2016. In silico toxicology: computational methods for the predictionof chemical toxicity. Wiley Interdiscip. Rev. Comput. Mol. Sci. 6 (2), 147–172. https://doi.org/10.1002/wcms.1240.

Raj, A., Kumar, S., Haq, I., Singh, S.K., 2014. Bioremediation and toxicity reduction in pulpand paper mill effluent by newly isolated ligninolytic Paenibacillus sp. Ecol. Eng. 71,355–362. https://doi.org/10.1016/j.ecoleng.2014.07.002.

Rajput, H., Changotra, R., Kumar Sangal, V., Dhir, A., 2020. Photoelectrocatalytic treatmentof recalcitrant compounds and bleach stage pulp and paper mill effluent using Au-TiO2 nanotube electrode. Chem. Eng. J. Press 127287. https://doi.org/10.1016/j.cej.2020.127287.

Ralph, J., Lundquist, K., Brunow, G., Lu, F., Kim, H., Schatz, P.F., Marita, J.M., Hatfield, R.D.,Ralph, S.A., Christensen, J.H., Boerjan,W., 2004. Lignins: natural polymers from oxida-tive coupling of 4-hydroxyphenyl-propanoids. Phytochem. Rev. 3 (1), 29–60. https://doi.org/10.1023/B:PHYT.0000047809.65444.a4.

Rasmussen, H., Tanner, D., Sørensen, H.R., Meyer, A.S., 2017. New degradation compoundsfrom lignocellulosic biomass pretreatment: routes for formation of potentoligophenolic enzyme inhibitors. Green Chem. 19, 464–474. https://doi.org/10.1039/c6gc01809b.

Ravi, K., Abdelaziz, O.Y., Nöbel, M., García-Hidalgo, J., Gorwa-Grauslund, M.F., Hulteberg,C.P., Lidén, G., 2019. Bacterial conversion of depolymerized Kraft lignin. Biotechnol.Biofuels 12 (1), 56. https://doi.org/10.1186/s13068-019-1397-8.

Reis, A.R., Tabei, K., Sakakibara, Y., 2014. Oxidation mechanism and overall removal ratesof endocrine disrupting chemicals by aquatic plants. J. Hazard. Mater. 265, 79–88.https://doi.org/10.1016/j.jhazmat.2013.11.042.

Riaz, M.R., Preston, G.M., Mithani, A., 2020. MAPPS: a web-based tool for metabolic path-way prediction and network analysis in the postgenomic era. ACS Syn. Biol. 9 (5),1069–1082. https://doi.org/10.1021/acssynbio.9b00397.

Rim, K.-T., 2020. In silico prediction of toxicity and its applications for chemicals at work.Toxicol. Environ. Health Sci. 12 (3), 191–202. https://doi.org/10.1007/s13530-020-00056-4.

Riyadi, F.A., Tahir, A.A., Yusof, N., Sabri, N.S.A., Noor, M.J.M.M., Akhir, F.N.M.D., Othman,N.A., Zakaria, Z., Hara, H., 2020. Enzymatic and genetic characterization of lignin de-polymerization by Streptomyces sp. S6 isolated from a tropical environment. Sci.Rep. 10 (1), 7813. https://doi.org/10.1038/s41598-020-64817-4.

Robles-González, I.V., Fava, F., Poggi-Varaldo, H.M., 2008. A review on slurry bioreactorsfor bioremediation of soils and sediments. Microb. Cell Fact. 7 (1), 5. https://doi.org/10.1186/1475-2859-7-5.

Ronen, Z., Abeliovich, A., 2000. Anaerobic-aerobic process for microbial degradation oftetrabromobisphenol A. Appl. Environ. Microbiol. 66 (6), 2372. https://doi.org/10.1128/AEM.66.6.2372-2377.2000.

Ropero, A.B., Alonso-Magdalena, P., Quesada, I., Nadal, A., 2008. The role of estrogen re-ceptors in the control of energy and glucose homeostasis. Steroids 73 (9–10),874–879. https://doi.org/10.1016/j.steroids.2007.12.018.

Roppola, K., Kuokkanen, T., Rämö, J., Prokkola, H., Ruotsalainen, J., 2009. Characterisationof organic fractions of pulp and paper mill wastewater with a manometric respiro-metric biochemical oxygen demandmethod and automatic chemical oxygen demandanalyses. Chem. Speciat. Bioavailab. 21 (2), 121–130. https://doi.org/10.3184/095422909X450533.

Rubilar, O., Diez, M.C., Gianfreda, L., 2008. Transformation of chlorinated phenolic com-pounds by white rot fungi. Crit. Rev. Environ. Sci. Technol. 38 (4), 227–268. https://doi.org/10.1080/10643380701413351.

Rucká, L., Nešvera, J., Pátek, M., 2017. Biodegradation of phenol and its derivatives byengineered bacteria: current knowledge and perspectives. World J. Microbiol.Biotechnol. 33 (9), 174. https://doi.org/10.1007/s11274-017-2339-x.

Sachan, P., Madan, S., Hussain, A., 2019. Isolation and screening of phenol-degrading bac-teria from pulp and paper mill effluent. Appl Water Sci 9, 100. https://doi.org/10.1007/s13201-019-0994-9.

Sáez-Jiménez, V., Acebes, S., Garcia-Ruiz, E., Romero, A., Guallar, V., Alcalde, M., Medrano,Francisco J., Martínez, Angel T., Ruiz-Dueñas, Francisco J., 2016. Unveiling the basis ofalkaline stability of an evolved versatile peroxidase. Biochem. J. 473 (13), 1917–1928.https://doi.org/10.1042/BCJ20160248.

Sanghvi, G., Thanki, A., Pandey, S., Singh, N.K., 2020. 17 — Engineered bacteria for biore-mediation. In: Pandey, V.C., Singh, V. (Eds.), Bioremediation of Pollutants. Elsevier,pp. 359–374 https://doi.org/10.1016/B978-0-12-819025-8.00017-X.

Santos, A., Mendes, S., Brissos, V., Martins, L.O., 2014. New dye-decolorizing peroxidasesfrom Bacillus subtilis and Pseudomonas putidaMET94: towards biotechnological appli-cations. Appl. Microbiol. Biotechnol. 98 (5), 2053–2065. https://doi.org/10.1007/s00253-013-5041-4.

Sappington, E.N., Balasubramani, A., Rifai, H.S., 2015. Polychlorinated dibenzo-p-dioxinsand polychlorinated dibenzofurans (PCDD/Fs) in municipal and industrial effluents.Chemosphere 133, 82–89. https://doi.org/10.1016/j.chemosphere.2015.04.019.

Saxena, G., Kishor, R., Purchase, D., Bharagava, R.N., Chandra, R., Dubey, N.K., Kumar, V.,2019. Phytoremediation of environmental pollutants. Environ. Earth Sci. 78 (14),418. https://doi.org/10.1007/s12665-019-8454-2.

Saxena, P., Singh, N.K., Harish, Singh, A.K., Pandey, S., Thanki, A., Yadav, T.C., 2020. 5— Re-cent advances in phytoremediation using genome engineering CRISPR-Cas9 technol-ogy. In: Pandey, V.C., Singh, V. (Eds.), Bioremediation of Pollutants. Elsevier,pp. 125–141 https://doi.org/10.1016/B978-0-12-819025-8.00005-3.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

Sayler, G.S., Ripp, S., 2000. Field applications of genetically engineeredmicroorganisms forbioremediation processes. Curr. Opin. Biotechnol. 11 (3), 286–289. https://doi.org/10.1016/S0958-1669(00)00097-5.

Sher, F., Yaqoob, A., Saeed, F., Zhang, S., Jahan, Z., Klemeš, J.J., 2020. Torrefied biomass fuelsas a renewable alternative to coal in co-firing for power generation. Energy 209,118444. https://doi.org/10.1016/j.energy.2020.118444.

Shi, L., Ge, J., Zhang, F., Nie, S., Qin, C., Yao, S., 2019. Difference in adsorbable organic hal-ogen formation between phenolic and non-phenolic lignin model compounds inchlorine dioxide bleaching. R. Soc. Open Sci. 6 (10), 191202. https://doi.org/10.1098/rsos.191202.

Shi, X., Xu, C., Hu, H., Tang, F., Sun, L., 2016. Characterization of dissolved organicmatter inthe secondary effluent of pulp and paper mill wastewater before and after coagula-tion treatment. Water Sci. Technol. 74 (6), 1346–1353. https://doi.org/10.2166/wst.2016.311.

Shrestha, R., Huang, G., Meekins, D.A., Geisbrecht, B.V., Li, P., 2017. Mechanistic insightsinto dye-decolorizing peroxidase revealed by solvent isotope and viscosity effects.ACS Catal. 7 (9), 6352–6364. https://doi.org/10.1021/acscatal.7b01861.

Shrotri, A., Kobayashi, H., Fukuoka, A., 2017. Chapter Two— Catalytic conversion of struc-tural carbohydrates and lignin to chemicals. In: Song, C. (Ed.), Advances in Catalysis.Academic Press, pp. 59–123 https://doi.org/10.1016/bs.acat.2017.09.002.

Sigman, R., Hilderink, H., Delrue, N., Braathen, N.A., Leflaive, X., 2012. Health and environ-ment. In: OECD (Ed.), OECD Environmental Outlook to 2050, pp. 207–273 https://doi.org/10.1787/env_outlook-2012-9-en.

Singh, A.K., Raj, A., 2020. Emerging and eco-friendly approaches for waste management: abook review. Environ. Sci. Eur. 32 (1), 107. https://doi.org/10.1186/s12302-020-00383-w.

Singh, A.K., Yadav, P., Bharagava, R.N., Saratale, G.D., Raj, A., 2019. Biotransformation andcytotoxicity evaluation of Kraft lignin degraded by ligninolytic Serratia liquefaciens.Front. Microbiol. 10, 2364. https://doi.org/10.3389/fmicb.2019.02364.

Singh, A.K., Chowdhary, P., Raj, A., 2020a. 13 — In silico bioremediation strategies for re-moval of environmental pollutants released from paper mills using bacterialligninolytic enzymes. In: Chowdhary, P., Raj, A., Verma, D., Akhter, Y. (Eds.), Microor-ganisms for Sustainable Environment and Health. Elsevier, pp. 249–285 https://doi.org/10.1016/B978-0-12-819001-2.00013-9.

Singh, A.K., Chowdhary, P., Raj, A., 2020b. Toxicity Evaluation of Paper Mill PollutantsUsing In Silico Toxicology Approach for Environment Safety, Contaminants andClean Technologies. CRC Press, pp. 65–91 https://doi.org/10.1201/9780429275852-5.

Singh, A.K., Muhammad, B., Iqbal, H.M.N., Raj, A., 2021a. Trends in predictive biodeg-radation for sustainable mitigation of environmental pollutants: recent progressand future outlook. Sci. Total Environ. 770, 144561. https://doi.org/10.1016/j.scitotenv.2020.144561.

Singh, A.K., Muhammad, B., Iqbal, H.M.N., Raj, A., 2021b. Lignin peroxidase in focus for cat-alytic elimination of contaminants — a critical review on recent progress and per-spectives. Int. J. Biol. Macromol. https://doi.org/10.1016/j.ijbiomac.2021.02.032 InPress.

Singh, J.S., Abhilash, P.C., Singh, H.B., Singh, R.P., Singh, D.P., 2011. Genetically engineeredbacteria: an emerging tool for environmental remediation and future research per-spectives. Gene 480 (1–2), 1–9. https://doi.org/10.1016/j.gene.2011.03.001.

Singh, R., Grigg, J.C., Qin, W., Kadla, J.F., Murphy, M.E.P., Eltis, L.D., 2013. Improvedmanganese-oxidizing activity of DypB, a peroxidase from a lignolytic bacterium.ACS Chem. Biol. 8 (4), 700–706. https://doi.org/10.1021/cb300608x.

Singh, S., Kang, S.H., Mulchandani, A., Chen, W., 2008. Bioremediation: environmentalclean-up through pathway engineering. Curr. Opin. Biotechnol. 19 (5), 437–444.https://doi.org/10.1016/j.copbio.2008.07.012.

Sitarz, A.K., Mikkelsen, J.D., Meyer, A.S., 2016. Structure, functionality and tuning up oflaccases for lignocellulose and other industrial applications. Crit. Rev. Biotechnol. 36(1), 70–86. https://doi.org/10.3109/07388551.2014.949617.

Soskolne, C.L., Sieswerd, L.E., 2010. Cancer risk associated with pulp and paper mills: a re-view of occupational and community epidemiology. Chron. Dis. Can. 29, 86–100. Doi:10.24095/hpcdp.29.S2.02.

Srinivasan, S., Sadasivam, S.K., Gunalan, S., Shanmugam, G., Kothandan, G., 2019. Applica-tion of docking and active site analysis for enzyme linked biodegradation of textiledyes. Environ. Pollut. 248, 599–608. https://doi.org/10.1016/j.envpol.2019.02.080.

Stefanakis, A.I., Thullner, M., 2016. Fate of phenolic compounds in constructed wetlandstreating contaminated water. In: Ansari, A.A., Gill, S.S., Gill, R., Lanza, G.R., Newman,L. (Eds.), Phytoremediation: Management of Environmental Contaminants. Vol. 4.Springer International Publishing, Cham, pp. 311–325. https://doi.org/10.1007/978-3-319-41811-7_16.

Sudarshan, K., Maruthaiya, K., Kotteeswaran, P., Murugan, A., 2017. Reuse the pulp andpaper industry wastewater by using fashionable technology. Appl Water Sci 7 (6),3317–3322. https://doi.org/10.1007/s13201-016-0477-1.

Sundaramoorthy, M., Gold, M.H., Poulos, T.L., 2010. Ultrahigh (0.93Å) resolution structureof manganese peroxidase from Phanerochaete chrysosporium: implications for thecatalytic mechanism. J. Inorg. Biochem. 104 (6), 683–690. https://doi.org/10.1016/j.jinorgbio.2010.02.011.

Taboada-Puig, R., Lu-Chau, T.A., Eibes, G., Feijoo, G., Moreira, M.T., Lema, J.M., 2015. Con-tinuous removal of endocrine disruptors by versatile peroxidase using a two-stagesystem. Biotechnol. Prog. 31 (4), 908–916. https://doi.org/10.1002/btpr.2116.

Tapscott, T., Guarnieri, M.T., Henard, C.A., 2019. Development of a CRISPR/Cas9 system forMethylococcus capsulatus in vivo gene editing. Appl. Environ. Microbiol. 85 (11).https://doi.org/10.1128/AEM.00340-19.

Tay, P.K.R., Nguyen, P.Q., Joshi, N.S., 2017. A synthetic circuit for mercury bioremediationusing self-assembling functional amyloids. ACS Syn. Biol. 6 (10), 1841–1850. https://doi.org/10.1021/acssynbio.7b00137.

20

Taylor, E.A., 2019. Lignin enzymology— recent efforts to understand lignin monomer ca-tabolism. In: Begley, H.-W.B.L. (Ed.), Comprehensive Natural Products III. Elsevier,pp. 373–398 https://doi.org/10.1016/B978-0-12-409547-2.14670-0.

Tekere, M., 2019. Microbial bioremediation and different bioreactors designs applied, bio-technology and bioengineering. IntechOpen, pp. 1–19 https://doi.org/10.5772/intechopen.83661.

Tekere, M., Read, J.S., Mattiasson, B., 2005. Polycyclic aromatic hydrocarbon biodeg-radation in extracellular fluids and static batch cultures of selected sub-tropicalwhite rot fungi. J. Biotechnol. 115 (4), 367–377. https://doi.org/10.1016/j.jbiotec.2004.09.012.

Thacker, N., Shahare, V., Das, S., Devotta, S., 2007. Dioxin formation in pulp and papermills of India. Environ. Sci. Pollut. Res. Int. 14, 225–226. https://doi.org/10.1065/espr2007.02.386.

Thakur, I., 2004. Screening and identification of microbial strains for removal of colourand adsorbable organic halogens in pulp and paper mill effluent. Process Biochem.39, 1693–1699. https://doi.org/10.1016/S0032-9592(03)00303-0.

Torén, K., Persson, B., Wingren, G., 1996. Health effects of working in pulp and papermills: malignant diseases. Am. J. Ind. Med. 29 (2), 123–130. https://doi.org/10.1002/(SICI)1097-0274(199602)29:2<111::AID-AJIM1>3.0.CO;2-V.

Uğurlu, M., Karaoğlu, M.H., 2009. Removal of AOX, total nitrogen and chlorinated ligninfrom bleached Kraft mill effluents by UV oxidation in the presence of hydrogen per-oxide utilizing TiO2 as photocatalyst. Environ. Sci. Pollut. Res. 16 (3), 265–273.https://doi.org/10.1007/s11356-008-0044-x.

Upadhyay, P., Shrivastava, R., Agrawal, P.K., 2016. Bioprospecting and biotechnological ap-plications of fungal laccase. 3 Biotech. 6 (1), 15. https://doi.org/10.1007/s13205-015-0316-3.

Urbaniak, M., Kiedrzyńska, E., Grochowalski, A., 2017. The variability of PCDD/F concen-trations in the effluent of wastewater treatment plants with regard to their hydrolog-ical environment. Environ. Monit. Assess. 189 (2), 1–13. https://doi.org/10.1007/s10661-017-5794-9.

Urgun-Demirtas, M., Stark, B., Pagilla, K., 2006. Use of genetically engineered microorgan-isms (GEMs) for the bioremediation of contaminants. Crit. Rev. Biotechnol. 26 (3),145–164. https://doi.org/10.1080/07388550600842794.

Vaidya, V., Carota, E., Calonzi, D., Petruccioli, M., D'Annibale, A., 2019. Production of lignin-modifying enzymes by Trametes ochracea on high-molecular weight fraction of olivemill wastewater, a byproduct of olive oil biorefinery. New Biotechnol. 50, 44–51.https://doi.org/10.1016/j.nbt.2019.01.007.

Vashi, H., Iorhemen, O.T., Tay, J.H., 2018. Degradation of industrial tannin and lignin frompulp mill effluent by aerobic granular sludge technology. J. Water Proc. Eng. 26,38–45. https://doi.org/10.1016/j.jwpe.2018.09.002.

Vecoli, C., Montano, L., Andreassi, M.G.J.E.S., Research, P., 2016. Environmental pollutants:genetic damage and epigenetic changes in male germ cells. Environ. Sci. Pollut. Res.Int. 23 (23), 23339–23348. https://doi.org/10.1007/s11356-016-7728-4.

Verma, M., Ekka, A., Mohapatra, T., Ghosh, P., 2020. Optimization of Kraft lignin decolori-zation and degradation by bacterial strain Bacillus velezensis using response surfacemethodology. J. Environ. Chem. Eng. 8 (5), 104270. https://doi.org/10.1016/j.jece.2020.104270.

Vilela, C.L.S., Bassin, J.P., Peixoto, R.S., 2018.Water contamination by endocrine disruptors:impacts, microbiological aspects and trends for environmental protection. Environ.Pollut. 235, 546–559. https://doi.org/10.1016/j.envpol.2017.12.098.

Wackett, L.P., 2013. The metabolic pathways of biodegradation. In: Rosenberg, E., DeLong,E.F., Lory, S., Stackebrandt, E., Thompson, F. (Eds.), The Prokaryotes: Applied Bacteri-ology and Biotechnology. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp. 383–393https://doi.org/10.1007/978-3-642-31331-8_76.

Wagle, D., Lin, C.-J., Nawaz, T., Shipley, H.J., 2020. Evaluation and optimization ofelectrocoagulation for treating Kraft paper mill wastewater. J. Environ. Chem. Eng. 8(1), 103595. https://doi.org/10.1016/j.jece.2019.103595.

Wang, G.-D., Li, Q.-J., Luo, B., Chen, X.-Y., 2004. Ex planta phytoremediation oftrichlorophenol and phenolic allelochemicals via an engineered secretory laccase.Nat. Biotechnol. 22 (7), 893–897. https://doi.org/10.1038/nbt982.

Wang, Q., Yang, M., Song, X., Tang, S., Yu, L., 2019. Aerobic and anaerobic biodegradationof 1,2-dibromoethane by a microbial consortium under simulated groundwater con-ditions. Int. J. Environ. Res. Publ. Health 16 (19), 3775. https://doi.org/10.3390/ijerph16193775.

Wang, W., Wang, L., Shao, Z., 2018. Polycyclic aromatic hydrocarbon (PAH) degradationpathways of the obligate marine PAH degrader Cycloclasticus sp. strain P1. Appl. En-viron. Microbiol. 84 (21), 1–15. https://doi.org/10.1128/AEM.01261-18.

Xiao, P., Kondo, R., 2020. Biodegradation and biotransformation of pentachlorophenol bywood-decaying white rot fungus Phlebia acanthocystis TMIC34875. J. Wood Sci. 66(1), 2. https://doi.org/10.1186/s10086-020-1849-6.

Xu, Z., Lei, P., Zhai, R., Wen, Z., Jin, M., 2019. Recent advances in lignin valorization withbacterial cultures: microorganisms, metabolic pathways, and bio-products.Biotechnol. Biofuels 12 (1), 32. https://doi.org/10.1186/s13068-019-1376-0.

Yadav, R., Kumar, V., Baweja, M., Shukla, P., 2018. Gene editing and genetic engineeringapproaches for advanced probiotics: a review. Crit. Rev. Food Sci. Nutr. 58 (10),1735–1746. https://doi.org/10.1080/10408398.2016.1274877.

Yin, K., Gao, C., Qiu, J.L., 2017. Progress and prospects in plant genome editing. Nat. Plants3, 17107. https://doi.org/10.1038/nplants.2017.107.

Yu, Y., Wu, B., Jiang, L., Zhang, X.-X., Ren, H.-Q., Li, M., 2019. Comparative analysis of tox-icity reduction of wastewater in twelve industrial park wastewater treatment plantsbased on battery of toxicity assays. Sci. Rep. 9 (1), 1–10. https://doi.org/10.1038/s41598-019-40154-z.

Zaidi, S.S., Mahfouz, M.M., Mansoor, S., 2017. CRISPR-Cpf1: a new tool for plant ge-nome editing. Trend. Plant Sci. 22 (7), 550–553. https://doi.org/10.1016/j.tplants.2017.05.001.

A.K. Singh, M. Bilal, H.M.N. Iqbal et al. Science of the Total Environment 777 (2021) 145988

Zakzeski, J., Bruijnincx, P.C., Jongerius, A.L., Weckhuysen, B.M., 2010. The catalytic valori-zation of lignin for the production of renewable chemicals. Chem. Rev. 110 (6),3552–3599. https://doi.org/10.1021/cr900354u.

Zdarta, J., Jankowska, K., Wyszowska, M., Kijeńska-Gawrońska, E., Zgoła-Grześkowiak, A.,Pinelo, M., Meyer, A.S., Moszyński, D., Jesionowski, T., 2019. Robust biodegradation ofnaproxen and diclofenac by laccase immobilized using electrospun nanofibers withenhanced stability and reusability. Mater. Sci. Eng. C Mater. Biol. Applic. 103,109789. https://doi.org/10.1016/j.msec.2019.109789.

Zhang, J., Ye, P., Chen, S., Wang, W., 2007. Removal of pentachlorophenol by immobilizedhorseradish peroxidase. Int. Biodeterior. Biodegrad. 59 (4), 307–314. https://doi.org/10.1016/j.ibiod.2006.09.003.

Zhang, J., Chen, Y., Brook, M.A., 2014. Reductive degradation of lignin and model com-pounds by hydrosilanes. ACS Sust. Chem. Eng. 2 (8), 1983–1991. https://doi.org/10.1021/sc500302j.

21

Zhang, J., Ma, L., Yan, Y., 2020. A dynamic comparison sustainability study of standardwastewater treatment system in the straw pulp papermaking process and printingand dyeing papermaking process based on the hybrid neural network and emergyframework. Water. 12, 1781–1810. https://doi.org/10.3390/w12061781.

Zheng, W., Colosi, L.M., 2011. Peroxidase-mediated removal of endocrine disrupting com-pound mixtures from water. Chemosphere 85 (4), 553–557. https://doi.org/10.1016/j.chemosphere.2011.06.064.

Zhong, M., Nie, Y., 2017. Types of Lignin and Extraction Processing, Functional Mate-rials From Lignin. World Scientific (Europe), pp. 29–47 https://doi.org/10.1142/9781786345219_0002.