Bacterial Physiology and Metabolism

Byung Hong KimKorea Institute of Science and Technology

Geoffrey Michael GaddUniversity of Dundee

Univeriiciits- ::;*.d Undes-bibiiothok Oarr>?">-^!(B ib l io t ' -e ' : ;." i : ' t •;;;<s

CAMBRIDGEUNIVERSITY PRESS

Contents in brief

I Introduction to bacterial physiology and metabolism page 1

2 I Composition and structure of prokaryotic cells

3 I Membrane transport - nutrient uptake and proteinexcretion 35

4 I Glycolysis 60

5 I Tricarboxylic acid (TCA) cycle, electron transport andoxidative phosphorylation 85

6 Biosynthesis and microbial growth 126

7 Heterotrophic metabolism on substrates other thanglucose 202

8

9

10

II

12

Anaerobic fermentation

Anaerobic respiration

Chemolithotrophy

Photosynthesis

Metabolic regulation

252

298

354

386

408

13 I Energy, environment and microbial survival 482

Contents

Preface page xxi

I I Introduction to bacterial physiology andmetabolism l

Further reading 4

2 Composition and structure of prokaryotic cells 7

2.1 Elemental composition 72.2 Importance of chemical form 8

2.2.1 Five major elements 82.2.2 Oxygen 92.2.3 Growth factors 10

2.3 Structure of microbial cells 102.3.1 Flagella and pili ^ 102.3.2 Capsules and slime layers 122.3.3 S-layer, outer membrane and cell wall 12

2.3.3.1 S-layer 132.3.3.2 Outer membrane 132.3.3.3 Cell wall and periplasm 17

2.3.4 Cytoplasmic membrane 212.3.4.1 Properties and functions 212.3.4.2 Membrane structure c 222.3.4.3 Phospholipids 232.3.4.4 Proteins 26

2.3.5 Cytoplasm 272.3.6 Resting cells 29

Further reading 30

3 I Membrane transport - nutrient uptake andprotein excretion 35

3.1 Ionophores: models of carrier proteins 353.2 Diffusion 373.3 Active transport and role of electrochemical gradients 373.4 ATP-dependent transport: ATP-binding cassette

(ABC) pathway ., 383.5 Group translocation 393.6 Precursor/product antiport " 403.7 Ferric ion (Fe(III)) uptake 41

CONTENTS

3.8 Export of cell surface structural components 433.8.1 Protein transport 43

3.8.1.1 General secretory pathway (GSP) 43

3.8.1.2 Twin-arginine translocation (TAT) pathway 45

3.8.1.3 ATP-binding cassette (ABC) pathway 46

3.8.2 Protein translocation across the outer membrane inGram-negative bacteria 463.8.2.1 Chaperone/usher pathway ~" 47

3.8.2.2 Type I pathway: ATP-binding cassette (ABC) pathway 47

3.8.2.3 Type II pathway 47

3.8.2.4 Type III pathway 49

3.8.2.5 Type IV pathway . 50

3.8.2.6 Type V pathway: autotransporter and proteins requiring

single accessory factors " 51"

Further reading 52

4 Glycolysis

4.1 EMP pathway4.1.1 Phosphofructokinase (PFK): key enzyme of the EMP

pathway

4.1.2 ATP synthesis and production of pyruvate

4.1.3 Modified EMP pathways

4.1.3.1 Methylglyoxal bypass

4.1.3.2 Modified EMP pathways in archaea

4.1.4 Regulation of the EMP pathway

4.1.4.1 Regulation of phosphofructokinase

4.1.4.2 Regulation of pyruvate kinase

4.1.4.3 Global regulation

4.2 Glucose-6-phosphate synthesis: gluconeogenesis4.2.1 PEP synthesis4.2.2 Fructose diphosphatase4.2.3 Gluconeogenesis in archaea4.2.4 Regulation of gluconeogenesis

4.3 Hexose monophosphate (HMP) pathway4.3.1 HMP pathway in three steps4.3.2 Additional functions of the HMP pathway

4.3.2.1 Utilization of pentoses4.3.2.2 Oxidative HMP cycle

4.3.3 Regulation of the HMP pathway4.3.4 F420-dependent glucose-6-phosphate dehydrogenase

4.4 Entner-Doudoroff (ED) pathway4.4.1 Glycolytic pathways in some Gram-negative bacteria4.4.2 Key enzymes of the ED pathway4.4.3 Modified ED pathways

60

61

61

63

64

64

65

66

66

67

67 >

6.7

676868696969707171717172727272

CONTENTS I ki

4.4.3.1 Extracellular oxidation of glucose by Gram-negative

bacteria . 72

4.4.3.2 Modified ED pathways in archaea , 74

4.5 Phosphoketolase pathways 744.5.1 Glucose fermentation by Leuconostoc mesenteroides 754.5.2 Bifidum pathway 77

4.6 Use of radiorespirometry to determine glycolytic pathways 78Further reading : 80

5 Tricarboxylic acid (TCA) cycle, electron transportand oxidative phosphorylation 85

5.1 Oxidative decarboxylation of pyruvate 855.2 Tricarboxylic acid (TCA) cycle 86

5.2.1 Citrate synthesis and the TCA cycle 875.2.2 Regulation of the TCA cycle 88

5.3 Replenishment of TCA cycle intermediates 885.3.1 Anaplerotic sequence 885.3.2 Glyoxylate cycle 89

5.3.2.1 Regulation of the glyoxylate cycle 905.4 Incomplete TCA fork and reductive TCA cycle 91

5.4.1 Incomplete TCA fork 915.4.2 Reductive TCA cycle 92

5.5 Energy transduction in prokaryotes 935.5.1 Free energy 93

5.5.1.1 AG° from the free energy of formation 94

5.5.1.2 AG° from the equilibrium constant 94

5.5.1.3 AGfromAG0' 95

5.5.1.4 AG0' from AG° ^ 95

5.5.2 Free energy of an oxidation/reduction reaction 955.5.2.1 Oxidation/reduction potential 955.5.2.2 Free energy from AE0' . 9 6

5.5.3 Free energy of osmotic pressure 975.5.4 Sum of free energy change in a series of reactions 97

5.6 Role of ATP in the biological energy transduction process 985.6.1 High energy phosphate bonds 995.6.2 Adenylate energy charge i 1005.6.3 Phosphorylation potential (AGp) 1015.6.4 Interconversion of ATP and proton motive force (Ap) 1015.6.5 Substrate-level phosphorylation (SLP) 102

5.7 Proton motive force (Ap) ' 1025.7.1 Proton gradient and membrane potential 1025.7.2 Acidophilicity and alkalophilicity 1035.7.3 Proton motive force in acidophiles ^ 1035.7.4 Proton motive force and sodium motive force

in alkalophiles 104

CONTENTS

5.8 Electron transport (oxidative) phosphorylation 1055.8.1 Chemiosmotic theory 1055.8.2 Electron carriers and the electron transport chain 105

5.8.2.1 Mitochondrial electron transport chain 1055.8.2.2 Electron carriers 1075.8.2.3 Diversity of electron transport chains in prokaryotes 1085.8.2.4 Inhibitors of electron transport phosphorylation (ETP) 1105.8.2.5 Transhydrogenase • 110

5.8.3 Arrangement of "electron carriers in theH+-translocating membrane 111,

5.8.3.1 Q.-cycle and Q.-loop- 1115.8.3.2 Proton pump 112

5.8.4 ATP synthesis 1125.8.4.1 ATPsynthase 1125.8.4.2 H+/O ratio ' 1135.8.4.3 H+/ATP stoichiometry - 114

5.8.5 Uncouplers c' 1145.8.6 Primary H+(Na+) pumps in fermentative metabolism 115

5.8.6.1 Fumarate reductase 1155.8.6.2 Na+-dependent decarboxylase 1155.8.6.3 Ap formation through fermentation product/H+

symport 1165.9 Other biological energy transduction processes 116

5.9.1 Bacterial bioluminescence 116, 5.9.2 Electricity as an energy source in microbes 117Further reading 118

6 Biosynthesis and microbial growth 126

6.1 Molecular composition of bacterial cells 1266.2 Assimilation of inorganic nitrogen 127

6.2.1 Nitrogen fixation ' • •- 1286.2.1.1 N2-fixing organisms 1286.2.1.2 Biochemistry of N2 fixation 1296.2.1.3 Bioenergetics of N2 fixation 1326.2.1.4 Molecular oxygen and N2 fixation ' 1326.2.1.5 Regulation of N2 fixation 134

6.2.2 Nitrate reduction 1356.2.3 Ammonia assimilation 137

6.3 Sulfate assimilation 1396.4 Amino acid biosynthesis 140

. 6.4.1 The pyruvate and oxaloacetate families 1406.4.2 The phosphoglycerate family 1416.4.3 The 2-ketoglutarate family 1416.4.4 Aromatic amino acids 1416:4.5 Histidine biosynthesis 1456.4.6 Regulation of amino acid biosynthesis 145

CONTENTS

6.5 Nucleotide biosynthesis 1456.5.1 Salvage pathway 1456.5.2 Pyrimidine nucleotide biosynthesis through a de novo

pathway - 1486.5.3 De novo synthesis of purine nucleotides 1496.5.4 Synthesis of dedxynucleotides 149

6.6 Lipid biosynthesis > , 1526.6.1 Fatty acid biosynthesis 152

6.6.1.1 Saturated acyl-ACP / 1536.6.1.2 Branched acyl-ACP ;^s- 1546.6.1.3 Unsaturated acyl-ACP 1546.6.1.4 Cyclopropane fatty acids / 1566.6.1.5 Regulation of fatty acid biosynthesis . 156

6.6.2 Phospholipid biosynthesis 1566.6.3 Isoprenoid biosynthesis 159

6.7 Heme biosynthesis 1596.8 Synthesis of saccharides and their derivatives 161

6.8.1 Hexose phosphate and UDP-sugar 1616.8.2 Monomers of rhurein . 1636.8.3 Monomers of teichoic acid i ' 1646.8.4 Precursor of lipopolysaccharide, O-antigen " 164

6.9 Polysaccharide biosynthesis and the assembly of cellsurface structures 1656.9.1 Glycogen synthesis 1656.9.2 Murein synthesis and cell wall assembly 167

6.9.2.1 Transport of cell wall precursor componentsthrough the membrane 167 ,

6.9.2.2 Murein synthesis 1676.9.2.3 Teichoic acid synthesis 1676.9.2.4 Cell wall proteins in Gram-positive bacteria 169

6.9.3 Outer membrane assembly , 1696.9.3.1 Protein translocation 1696.9.3.2 Lipopolysaccharide (LPS) translocation 169

J * '

6.9.3.3 Phospholipid translocation 1706.9.4 Cytoplasmic membrane (CM) assembly 170

6.10 Deoxyribonucleic acid (DNA) replication 1706.10.1 DNA replication ' 170

6.10.1.1 RNA primer t 1716.10.1.2 Okazaki'fragment 1726.10.1.3 DNA polymerase 172

6.10.2 Spontaneous mutation ^ 1736.10.3 Post-replicational modification 1736.10.4 Chromosome segregation , 173

6.11 Transcription ' , • 1746.11.1 RNA synthesis " 1746.11.2 Post-transcriptional processing 174

xiv CONTENTS

6.12 Translation 1756.12.1 Amino acid activation 1766.12.2 Synthesis of peptide: initiation, elongation and

termination 1766.12.2.1 Ribosomes 1776.12.2.2 Initiation and elongation 1776.12.2.3 Termination 178

6.12.3 Post-translational modification and protein folding 1786.13 Assembly of cellular structure 181

6.13.1 Flagella 181/-.•'• 6.13.2 Capsules and slime 182

6.13.3 Nucleoid assembly 1826.13.4 Ribosome assembly 182

6.14 Growth . 1826.14.1 Cell division 183

6.14.1.1 Binary fission 1836.14.1.2 Multiple intracellular offspring 1846.14.1.3 Multiple offspring by multiple fission 1856.14.1.4 Budding 187

6.14.2 Growth yield 1876.14.3 Theoretical maximum YATP 1896.14.4 Growth yield using different electron acceptors and

maintenance energy 189

6.14.5 Maintenance energy 192Further reading 193

7 I Heterotrophic metabolism on substratesother than glucose 202

7.1 Hydrolysis of polymers 2027.1.1 Starch hydrolysis 2027.1.2 Cellulose hydrolysis 2037.1.3 Other polysaccharide hydrolases 2047.1.4 Disaccharide phosphorylases 2057.1.5 Hydrolysis of proteins, nucleic acids and lipids 206

7.2 Utilization of sugars " 2067.2.1 Hexose utilization 2067.2.2 Pentose utilization 207

7.3 Organic acid utilization 2087.3.1 Fatty acid utilization 2087.3.2 Organic acids more oxidized than acetate ' 210

7.4 Utilization of alcohols and ketones 2137.5 Amino acid utilization 214

7.5.1 Oxidative deamination 2157.5.2 Transamination 2157.5.3 Amino acid dehydratase 2157.5.4 Deamination of cysteine and methionine 216

CONTENTS

7.5.5 Deamination products of amino acids 2177.5.6 Other amino acids 220

7.6 Degradation of nucleic acid bases 2207.7 Oxidation of aliphatic,hydrocarbons 2237.8 Oxidation of aromatic compounds 225

7.8.1 Oxidation of aromatic amino acids 2257.8.2 Oriho and tneta cleavage, and the gentisate pathway 2277.8.3 Oxygenase and aromatic compound oxidation 229

7.9 Utilization of me thane and methano l 2297.9.1 Methanotrophy and niethylotrophy 2297.9.2 Methanotrophy 230

7.9.2.1 Characteristics ofmethanotrophs ,, 2307.9.2.2 Dissimilation of methane by methanotrophs 233

7.9.3 Carbon assimilation by methylotrophs 2357.9.3.1 Ribulose monophosphate (RMP) pathway 2357.9.3.2 Serine-isocitrate lyase (SIL) pathway ~ 2367.9.3.3 Xylulose monophosphate (XMP) pathway 240

7.9.4 Energy efficiency in Cl metabolism 2417.10 Incomplete oxidation 241

7.10.1 Acetic acid bacteria 2417.10.2 Acetoin and butanediolx 2427.10.3 Other products*of aerobic metabolism 243

Further reading 244

8 I Anaerobic fermentation 252

8.1 Electron acceptors used in anaerobic metabolism 252

8.1.1 Fermentation and anaerobic respiration 2528.1.2 Hydrogen in fermentation , 252

8.2 Molecular oxygen and anaerobes 2538.3 Ethanol fermentation ~ 2558.4 Lactate fermentation >. • ~ 257

8.4.1 Homolactate fermentation 2578.4.2 Heterolactate fermentation _ 2578.4.3 Biosynthesis in lactic acid bacteria (LAB) 2598.4.4 Oxygen metabolism in LAB- 2608.4.5 Lactate/H+ symport 2608.4.6 LAB in fermented food 260

8.5 Butyrate and ace tone-butanol -e thanol fermentat ions 2638.5.1 Butyrate fermentation • 263

8.5.1.1 Phosphoroclastic reaction 2638.5.1.2 Butyrate formation 2648.5.1.3 Lactate fermentation by Ctostridmm butyricum : 265

8.5.1.4 Clostridium butyricum as a probiotic _ 2688.5.1.5 Non-butyrate clostridial fermentation 268

8.5.2 Acetone-butanol-ethanol fermentation 2698.5.3 Fermentation balance 1 271

CONTENTS

-8.6 Mixed acid and butanediol fermentation 2728.6.1 Mixed acid fermentation 2728.6.2 Butanediol fermentation 2738.6.3 Citrate fermentation by facultative anaerobes 2758.6.4 Anaerobic enzymes 277

8.7 Propionate fermentation 2788.7.1 Succinate-propionate pathway 2788.7.2 Acrylate pathway 280

8.8 Fermentation of amino acids and nucleic acid bases 2818.8.1 Fermentation of individual amino acids 2818.8.2 Stickland reaction 2868.8.3 Fermentation of purine and pyrimidine bases 287

8.9 Fermentation of dicarboxylic acids 2878.10 Hyperthermophilic archaeal fermentation 2878.11 Degradation of xenobiotics under fermentative conditions 289

Further reading 290

Anaerobic respiration 298

9.1 Denitrification 2999.1.1 Biochemistry of denitrification 299

9.1.1.1 Nitrate reductase 3009.1.1.2 Nitrite reductase 3029.1.1.3 Nitric oxide reductase and nitrous oxide reductase 302J

9.1.2 ATP synthesis in denitrification 302.9.1.3 Regulation of denitrification 3039.1.4 Denitrifiers other than facultatively anaerobic

chemoorganotrophs 304

9.1.5 Oxidation of xenobiotics under denitrifying conditions 3069.2 Metal reduction 306

. 9.2.1 Fe(III) and Mn(IV) reduction 306

9.2.2 Microbial reduction of other metals 3099.2.3 Metal reduction and the environment 309

9.3 Sulfidogenesis 3109.3.1 Biochemistry of sulfidogenesis 312

9.3.1.1 Reduction ofsulfate and sulfur • - ; . 3129.3.1.2 Carbon metabolism 313

9.3.2 Electron transport and ATP yield in sulfidogens 3179.3.2.1 Incomplete oxidizers 3179.3.2.2 Complete oxidizers 318

9.3.3 Carbon skeleton supply in sulfidogens 3189.3.4 Oxidation of xenobiotics under sulfidogenic conditions 320

9.4 Methanogenesis 3209.4.1 Methanogens 320

9.4.1.1 Hydrogenotrophic methanogens 320i 9.4.1.2 Methylotrophic methanogens 322

9.4.1.3 Aceticlastic methanogens 322

CONTENTS

9.4.2 Coenzymes in methanogens . 3229.4.3 Methanogenic pathways - 324

9.4.3.1 Hydrogenotrophic methanogenesis 3249.4.3.2 Methylotrophic methanogenesis ,• . ! 3259.4.3.3 Aceticlastic methanogenesis i 326

9.4.4 Energy conservation in methanogenesis 3279.4.5 Biosynthesis in methanogens 328

9.5 Homoacetogenesis 3309.5.1 Homoacetogens 3309.5.2 Carbon metabolism in homoacetogens 330

9.5.2.1 Sugar metabolism 3309.5.2.2 Synthesis of carbon skeletons for biosynthesis

in homoacetogens 3339.5.3 Energy conservation in homoacetogens 334

9.6 Dehalorespiration 3349.6.1 Dehalorespiratory organisms 3359.6.2 Energy conservation in dehalorespiration 336

9.7 Miscellaneous electron acceptors 3369.8 Syntrophic associations 337

9.8.1 Syntrophic bacteria 3379.8.2 Carbon metabolism in syntrophic bacteria 3399.8.3 Facultative syntrophic associations 340

9.9 Element cycling under anaerobic conditions 3409.9.1 Oxidation of aromatic hydrocarbons under anaerobic

conditions 3419.9.2 Transformation of xenobiotics under anaerobic conditions 343

Further reading ' 345

10 I Chemolithotrophy 354

10.1 Reverse electron transport * 35410.2 Nitrification " ' ^ 355

10.2.1 Ammonia oxidation 35610.2.2 Nitrite oxidation '. 35710.2.3 Anaerobic nitrification 358

10.3 Sulfur bacteria and the oxidation of sulfur compounds 35810.3.1 Sulfur bacteria 35810.3.2 Biochemistry of sulfur compound oxidation 36010.3.3 Carbon metabolism in colourless sulfur bacteria 362

10.4 Iron bacteria: ferrous iron oxidation s 36210.5 Hydrogen oxidation ' 364

10.5.1 Hydrogen-oxidizing bacteria 364

10.5.2 Hydrogenase 36410.5.3 Anaerobic H2-oxidizers ^ 36510.5.4 CO2 fixation in H2-oxidizers 366

10.6 Carbon monoxide oxidation: carboxydobacteria 36610.7 Chemolithotrophs using other electron donors 367

CONTENTS

10.8 CO2 fixation pathways in chemolithotrophs 368r ,10:8.1 Calvin cycle 368' ' ' 10.8.1.1 Key enzymes of the Calvin cycle 370

10.8.1.2 Photorespiration 37210.8.2 Reductive TCA cycle 37310.8.3 Anaerobic CO2 fixation through the acetyl-CoA pathway 37410.8.4 CO2 fixation through the 3-hydroxypropionate cycle 37510.8.5 Energy expenditure in CO2 fixation 377

10.9 Chemolithotrophs: what makes them unable to useorganics? 377

Further reading 379

I I I Photosynthesis , 386

11.1 Photosynthetic microorganisms 38611.1.1 Cyanobacteria 38711.1.2 Anaerobic photosynthetic bacteria 38711.1.3 Aerobic anoxygenic phototrophic bacteria 388

11.2 Photosynthetic pigments 38911.2.1 Chlorophylls 39011.2.2 Carotenoids 39011.2.3 Phycobiliproteins 39211.2.4 Pheophytin 39211.2.5 Absorption spectra of photosynthetic cells 393

11.3 Photosynthetic apparatus 39411.3.1 Thylakoids of cyanobacteria 394

' 11.3.2 Green bacteria 39511.3.3 Purple bacteria 39511.3.4 Heliobacteria and aerobic anoxygenic phototrophic

bacteria 39511.4 Light reactions 396

11.4.1 Properties of light 39711.4.2 Excitation of antenna molecules and resonance transfer 39711.4.3 Electron transport 398

11.4.3.1 Photosystem I and II in cyanobacteria 39811.4.3.2 Green sulfur bacteria • 39811.4.3.3 Purple bacteria 40011.4.3.4 Aerobic anoxygenic photosynthetic bacteria 401

11.5 Carbon metabolism in phototrophs 401113.1 CO2 fixation . . 40111.5.2 Carbon metabolism in photoorganotrophs 402

11.5.2.1 Purple bacteria, heliobacteria and aerobicanoxygenic photosynthetic bacteria 402

11.5.2.2 Green sulfur bacteria 40311.5.2.3 Cyanobacteria 403

11.6 Photophosphorylation in halophilic archaea 403Further reading 405

CONTENTS

12 Metabolic regulation 408

12.1 Mechanisms regulating enzyme synthesis 40812.1.1 Regulation of transcription by promoter structure

and sigma (a) factor activity 40912.1.2 Induction of enzymes 411

12.1.2.1 Inducible and constitutive enzymes 411

12.1.2.2 Enzyme induction . 412

12.1.2.3 Positive and negative control 413

12.1.3 Catabolite repression 41312.1.3.1 Carbon catabolite repression by the cAMP-CRP

complex 41412.1.3.2 Catabolite repressor/activator 41512.1.3.3 Carbon catabolite repression in Gram-positive

bacteria with a low G + C content 41712.1.4 Repression and attenuation by final metabolic products 419

12.1.4.1 Repression " 41912.1.4.2 Attenuation , 420

12.1.5 Regulation of gene expression by multiple end products 42312.1.6 Termination and antitermination 424

12.1.6.1 Termination and antitermination aided by protein 424

12.1.6.2 Termination and antitermination aided by tRNA 42612.1.6.3 Termination and antitermination aided by

metabolites 42812.1.7 Two-component systems with sensor-regulator proteins 42812.1.8 Autogenous regulation J X 42812.1.9 Post-transcriptional regulation of gene expression 430

12.1.9.1 RNA stability 43012.1.9.2 mRNA structure and translational efficiency 43112.1.9.3 Modulation of translation and stability of mRNA

by protein 43112.1.9.4 Modulation of translation and stability of mRNA

by small RNA arid small RNA-proteincomplex: riboregulation 433

12.2 Global regulation: responses to environmental stress 43512.2.1 Stringent response . • 43712.2.2 Response to ammonia limitation ^ 43912.2.3 Response to phosphate limitation: the pho system 44112.2.4 Regulation by molecular oxygen in facultative

anaerobes 44212.2.4.1 arc system ^ 443

12.2.4.2 fnr system . 444

12.2.4.3 RegB/RegA system in purple non-sulfur

photosynthetic bacteria ,. 445

12.2.5 Oxidative stress 44512.2.6 Heat shock response 44612.2.7 Cold shock response 448

XX CONTENTS

s 12.2.8 Quorum sensing 45212.2.9 Response to changes in osmotic pressure 45312.2.10 Other two-component systems 45412.2.11 Chemotaxis - 45512.2.12 Adaptive mutation 457

12.3 Regulation through modulation of enzymeactivity: fine regulation 45912.3.1. Feedback inhibition and feedforward activation 45912.3.2 Enzyme activity modulation through structural

changes 46012.3.2.1 Phosphorylation 461

12.3.2.2 Adenylylation 461

12.3.2.3 Acetylation . 462

12.3.2.4 Other chemical modifications 463

12.3.2.5 Regulation through physical modification and

dissociation/association 463

12.4 Metabolic regulation and growth 46412.4.1 Regulation in central metabolism 46412.4.2 Regulatory network 46412.4.3 Growth rate and regulation . 466

12.5 Secondary metabolites 46612.6 Metabolic regulation and the fermentation industry 467

12.6.1 Fermentative production of antibiotics 46712.6.2 Fermentative amino acid production 467

Further reading 468

13 Energy, environment and microbial survival 482

13.1 Survival and energy 48213.2 Reserve materials in bacteria 483

13.2.1 Carbohydrate reserve materials: glycogen and trehalose 48313.2.2 Lipid reserve materials 484

13.2.2.1 Poly-/3-hydroxyalkanoate (PHA) 485

13.2.2.2 Triacylglyceride (TAG) 486

13.2.2.3 Wax ester and hydrocarbons 486

13.2.3 Polypeptides as reserve materials ^48713.2.4 Polyphosphate 488

13.3 Resting cells 48913.3.1 Sporulation in Bacillus subtUis 49013.3.2 Cysts 49013.3.3 Viable but non-culturable (VBNC) cells 49013.3.4 Nanobacteria 49213.3.5 Programmed cell death (PCD) in bacteria 492

Further reading 493

Index 496