INDEX

Aaptamine, 53Aaptos aaptos, 53ABC transporter genes, nonactin and, 202Abies grandies, 26Abietadienal, in diterpene resin acid biosynthesis,

137Abietadiene, in diterpene resin acid biosynthesis,

137Abietadienol, in diterpene resin acid

biosynthesis, 137Abietanes, 17, 18Abietic acid, 17, 18

biosynthesis of, 137Abraxane, 332Abscisic acid, 14–15, 17ABT594, 300Acacia farnesiana, 14Acanthella carvenosa, 58Acarbose, 94Acarviostatin, 94Acceptor ACP, 181Acetate, as plant biosynthetic building block, 3, 4Acetate pathway

plant products from, 6–7shikimate pathway and, 20, 22

Acetoacetyl-CoA, 178

Natural Products in Chemical Biology, First Edition. Edited by Natanya Civjan.© 2012 John Wiley & Sons, Inc. Published 2012 by John Wiley & Sons, Inc.

Acetogenins, 33Acetyl coenzyme A (acetyl–CoA), 6, 7, 151, 178

in isoprenoid cofactor biosynthesis, 254, 255Acetylnorajmaline, 218Acetyltransferase (AT) domains, 149, 150, 152,

153, 154, 155, 165, 166, 179–180, 182Achilllea filipedulina, 13“A” class, of KR domains, 169, 172, 173Acremonium chrysogenum, 271, 278Acremonium strictum, 150, 152Actinodaphe longifolia, 14Actinomadura madurae, 99Actinomadura pelletieri, 99Actinomycetes, 306

enzyme inhibitors produced by, 86immunosuppressant pyrrole compounds from,

99natural products from, 65–66

Actinomycin D, 339, 340Actinomycin family, 78, 303Actinoplanes, 71, 94Actinoplanes teichomyceticus, 71Actinorhodin, 276Actinorhodin PKS, 154Activation, in nonribosomal peptide synthesis,

112

389

390 INDEX

Aculeacin A, 76Acyclic monoterpenes, 9Acyclovir, 299Acylation, in antibiotic biosynthesis, 276Acyl carrier protein (ACP), 115, 165

in fungal polyketide biosynthesis, 145–146,149, 150, 151, 152, 154, 156

Acyl carrier protein domain, 165, 166, 167, 172,173, 174, 178, 179–180, 181, 182

for nanchangmycin, 197–198for nonactin, 201

Acyl CoA, 149nonactin and, 201

Acyltransferase (AT) linkage, 165Acyltransferases, in antibiotic biosynthesis, 277Adenosine, in caffeine biosynthesis, 225S-Adenosylmethionine (SAM), in fungal

polyketide biosynthesis, 146Adenylation (A) domain, 179–180

exchange of, 119in nonribosomal peptide synthesis, 112,

114–115NRPS module, 158in producing novel peptides, 119–120

Adocia, 58, 59Adociasulfate-2, 59Adriamycin, 81, 82, 325, 336Adriatoxin, 202Aflatoxin, 151Aflatoxin B1, 144, 147Ageladine A, 48, 57Agelas, 57Agelas nakamurai, 48Agelas oroides, 48Agelas sceptrum, 48Agricultural benefits, of natural products, 66Agriculture

antibiotics important in, 271natural products in, 66

Agrobacterium aurantiacum, 87AIDS (acquired immunodeficiency syndrome),

365Ajmalan, 217Ajmalicine, 218, 219–220Ajmaline, 216–219Akiyama, Toshiyuki, ix, 351Alanine

in biotin biosynthesis, 253, 254in pantothenate biosynthesis, 249, 251

Aldoses, 5Alexandrium catenella, 52Alexandrium tamarense, 52Algae

amino acid derivatives from, 43

coenzymes from, 240–241fatty acid derivatives from, 33marine natural products from, 32monoterpenoids and sesquiterpenoids from, 55terpenoids from, 55

Aliphatic amino acids, alkaloids from, 23–24Alkaloids, 209–237

biochemistry of, 209biology of, 210diversity of, 22–23, 24–25, 209isoquinoline, 209, 210–215in marine natural products, 47–55as natural plant products, 22–25purine, 209, 210, 224–226terpenoid indole, 209, 210, 216–222tropane, 209, 210, 222–224

3-Alkylpiperidines, in marine natural products,47–48

17-Allylamino-geldanamycin (17-AAG), 336,338

Aloe, 7Aloe arborescens, 26Aloe-emodin, 6–7, 26α-carbon, atypical polyketide domains and,

175–176α-glucosidase inhibition, 94α-tocopherol, 255, 256alt5 gene, 158Alternapyrone, 157, 158Alternaria, 92Alternaria alternata, 90Alternaria solani, HR PKS from, 157–158Alternaric acid, 157, 158Alternariol, 143, 147Alternative medicine, 351–352Alteromonas rubra, 99Alzheimer’s agents, 301American ginseng, 370, 371, 372–373Amijidictyol, 563-Amino-1-hydroxyacetone phosphate, in

pyridoxal phosphate biosynthesis, 247, 249Amino acid derivatives, in marine natural

products, 43–45, 46Amino acids

alkaloids from, 22, 23–24, 24–25in antibiotic biosynthesis, 272–273aromatic, 20, 24–25in biochemical and metabolic terpenoid

engineering, 139in nonribosomal peptides, 111, 112

3-Aminobactamic acid, 674-Aminobenzoate, 2454-Aminobutanal, 223Aminocoumarins, in antibiotic biosynthesis, 277

INDEX 391

Aminoglycoside antibiotics, 273, 275–276, 278Aminoglycosides, 293Aminoimidazole ribotide, in thiamine

pyrophosphate biosynthesis, 245, 247, 248δ-Aminolevulinic acid, 244

tetrapyrroles from, 2436-Aminopenicillanic acid, 67, 292Amorphadiene, 298, 299

in artemisinin biosynthesis, 134Amorphane, 16Amoxicillin, 68, 292, 293Amphidinium, 36, 38Amphidinolides, 38Amphidinols, 36–37Amphimedine, 49Amphimedon, 49Amphotericin B, 271Amphotericin B, 73–75, 297Amycolatopsis mediterranei, 70, 271Amycolatopsis orientalis, 71, 271Amylose, 5, 6Anabasine, 24Analgesics, isoquinoline alkaloids as, 210Anethole, 22Anethum graveolens, 12Angiotensin-I-converting enzyme (ACE), 86–87,

309Anhydrovinblastine, 219

in vinblastine biosynthesis, 221Anidulafungin, 77, 297, 298Animals

GTP-related coenzymes biosynthesized in, 245pantothenate biosynthesis and, 249tetrapyrrole biosynthesis and, 243vitamins in, 239

Anions, ionophores as, 190–191Ansamycins, 68–70, 91, 272Anthocyanidins, 22, 23Anthracyclines, 303, 336, 337

antitumoral, 81–82Anthraquinone derivatives, 43Anthraquinones, 6–7Antibacterial agents, 291–296. See also

AntibacterialsAntibacterial polyketides, 68–71, 72Antibacterials

economic importance of, 66among microbial natural products, 66–73,

74–75Antibiotic 1233A, 91Antibiotic biosynthesis, 269, 270–274, 274–279

tools and techniques for studying, 279–281Antibiotic-producing organisms, genome

sequencing of, 270

Antibiotics, 269–285defined, 270diversity and applications of, 269–270,

270–271industrial production of, 273isoquinoline alkaloids as, 210macrotetrolides as, 200medically and agriculturaly important, 271monensins as, 194nanchangmycin as, 197among nonribosomal peptides, 111peptide, 71–73, 74–75polyene, 73–76polyketide polyethers as, 191

Antibiotic TA, HMGS-containing biosyntheticpathway for, 177

Anticancer agents. See also Antineoplastic agentsdefined, 352natural products as, 325–349overview of, 326plant-derived, 352–365that target proteins, 326–338that target RNA/DNA, 338–341

Antifungal agents/compounds, 296–297, 298gambieric acids as, 193among microbial natural products, 73–77

Anti-HIV compounds, 365–369Anti-infective drug targets, coenzyme

biosynthesis enzymes as, 261Antimalarial activity, 192Antimalarials, 297–298, 299Antineoplastic agents, 301–307. See also

Anticancer agents; Antitumoral entries;Antitumor compounds

defined, 352Antiobesity pharmaceuticals, 300–301Antipain agents, 85–86, 299–300Antiparasitic agents, 311–312

among microbial natural products, 82–84, 85Antiparasitical macrolides, 82–83Antiparasitical polyethers, 83–84, 85Antitumoral anthracyclines, 81–82Antitumoral peptides, 78–79Antitumoral polyketides, 81, 82Antitumoral pyrrole compounds, 79–81Antitumoral steroid alkaloids, 79, 80Antitumor compounds. See also Antineoplastic

agentsdefined, 352among microbial natural products, 77–82plant-derived, 352–365

Antivirals, 298–299Apicidin, 312–313Apicoplasts, 259

392 INDEX

Apigenin, 22, 23Aplidine, 46, 47Aplidium albicans, 46Aplydilactone, 32–33Aplyronines, 39Aplysia kurodai, 32, 39Apoenzymes, 259

iron/sulfur clusters and, 243apo-nanchangmycin, 199Apoptosis, 327, 342Ara-A, 299Arabidopsis, 132Arabidopsis thaliana, 222

terpenoid-synthase-encoding genes of, 129Arabinose, 5

in vitamin C biosynthesis, 251–252Arabinose-containing nucleosides, 31Arcaine backbone, 53Archaea, tetrapyrrole biosynthesis and, 243Archaeal coenzymes, biosynthesis of, 257Archaebacteria, 257Arginine, in tropane alkaloid biosynthesis, 222Aromatic amino acids, 20

alkaloids derived from, 24–25Aromatic cyclohexane monoterpenes, 12Aromatic natural products, 20Aromatic polyketides

in marine natural products, 43in plants, 6–7

Arsenic compounds, in marine natural products,32

Arsenobetaines, in marine natural products, 32Arsenosugars, in marine natural products, 32Arteether, 370Artemether, 298, 299, 370Artemisia, 12Artemisia annua, 26, 130, 134, 298

in folkloric medicine, 369–370Artemisia frangrans, 9Artemisin, 8, 127Artemisinic acid, 298, 299

in artemisinin biosynthesis, 134Artemisinin, 26, 130, 298, 370

biosynthesis of, 134Artemisinin derivatives, 369–370Arthrofactin, 118Arthropods, antiparasitics against, 82Ascidian peptides, 46, 47Ascididemin, 49Ascorbic acid, 5. See also Vitamin C

biosynthesis of, 251–252AS EC145 R, 353, 354Asian ginseng, 370, 371–372Aspartate

in pantothenate biosynthesis, 249, 251in pyridine nucleotide biosynthesis, 249, 250

Aspergillus, lipopeptides against, 76Aspergillus aculeatus, 76Aspergillus alliaceus, 312Aspergillus nidulans, 152, 155, 156, 271, 297Aspergillus niger, 87, 149Aspergillus oryzae, 152, 153, 157Aspergillus parasiticus, 151Aspergillus regulovalvus, 76Aspergillus terreus, 93, 150, 156, 148, 309Asperlicin, 312Asperula odorata, 10Asperuloside, 10Aspidosperma, 217Aspirin, isolation of, 290Assembly cycle, in fungal polyketide

biosynthesis, 145–146Atmospheric chemistry, isoprene in, 132Atorvastatin, 309, 310ATP (adenosine triphosphate), 240

in nonribosomal peptide synthesis, 114, 115ATP hydrolysis, in self-protection against

antibiotics, 274Atropa, 222Atropa belladonna, 23, 224Atropine, isolation of, 290Atypical PKS domains, 175–182Augmentin®, 293Aurasperone A, 87, 88Auristatin PE, 305, 306Austin, 144, 147Autoimmune diseases, 261Autotrophic organisms, coenzyme biosynthesis

in, 240–241Autumnaline, 25Avalos, Mariana, ix, 65Avarol, 56Avatec®, 191–192Avermectins, 82–83, 311Avilamycin, 275Axinella cannabina, 57Axinella infundibula, 59Axinelloside A, 59Axisonitrile-1, 57Ayurveda, 289Ayurvedic medicine, 351Azaspiracids, 36Azaspiracid shellfish poisoning, 36Azithromycin, 294, 295Azocines, 79, 80AZT, 367Aztreonam, 67, 68, 293Azumamides, 46

INDEX 393

Babylonia japonica, 51Baccatin III, 17, 18

in Taxol® biosynthesis, 135Bacher, Adelbert, ix, 239Bacillaene, 170, 173, 176, 181, 182

HMGS-containing biosynthetic pathway for,177

Bacilli, natural products from, 65–66Bacillibactin, 113, 114, 117Bacillus amyloiquefaciens, HMGS-containing

biosynthetic pathway of, 177Bacillus brevis, 73Bacillus polymyxa, 73Bacillus subtilis, 114, 181, 182, 247

HMGS-containing biosynthetic pathway of,177

Bacitracin, 113, 116, 117, 118synthesis of, 114

Bac series synthetases, 114Bacteria, 262. See also Antibacterial polyketides

antibiotic biosynthesis among, 270–271antibiotics against, 269antibiotics from, 270β-lactams from, 67–68in biochemical and metabolic terpenoid

engineering, 139coenzyme biosynthesis in, 259fungal polyketide biosynthesis and, 145growing number of resistant, 118guanidine alkaloids from, 52ionophores in controlling, 192marine natural products from, 32medically and agriculturaly important

antibiotics produced by, 271natural products from, 65–66peptide antibiotics against, 71–73, 74–75polyketides from, 143pyridine nucleotide biosynthesis in, 249tetrapyrrole biosynthesis and, 243thiamine pyrophosphate biosynthesis in,

245–247, 248Bacterial diseases, controlling, 165Bacterial modular PKS systems, 157

TE domain in, 156Bacterial modular polyketide synthases, in fungal

polyketide biosynthesis, 148Bacteriocins, 271Balanol, 88Balhimycin, 116Bassianolide, 100, 101Bastadins, 44, 45Batzella, 50, 52Batzelladines, 52Batzelline A, 49, 50

“B” class, of KR domains, 169, 173Beauveria bassiana, 100Beauvericin, 100Bengamides, 41, 42Benzoic acid derivatives, 20Benzonaphthyridine alkaloids, 53Benzophenanthridines, 211, 213

in sanginarine biosynthesis, 213–214Benzylisoquinoline alkaloid, 213Benzylisoquinolines, 25Benzyltetrahydroisoquinolines, 25Berberines, 210, 211, 212, 213

biosynthesis of, 213in morphine biosynthesis, 215

Bergapten, 22, 23Bergmen cyclization, 340β-branching, 163β-carbon, atypical polyketide domains and,

175–176β-carotene, 253, 255, 262

biosynthesis of, 256β-ketoacyl reductase (KR), in fungal polyketide

biosynthesis, 146, 154β-ketones, 167–168, 171, 174, 178β-lactamases, 67–68, 292–293β-lactams. See b-lactams (β-lactams)Betulinic acid, 368Betulinic acid derivatives, 367–369Bevirimat, 368, 369Bialaphos, 90, 271Bicyclic cyclobutane monoterpenoids, 12, 13Bicyclic cyclopentane monoterpenoids, 12,

13–14Bicyclic cyclopropane monoterpenoids, 12, 13Bicyclic sesquiterpenoids, 16, 17Bicycloelemene, 15, 17Bioactivity-directed fractionation and isolation

(BDFI), 351, 365Bioassay methods, 352. See also Biological

assaysBiochemical engineering, in studying terpenoids,

139Biofuel production, isoprene in, 132Bioinformatics, antibiotics and, 270Biological assays, 291. See also Bioassay

methodsBiologically active compounds

alkaloids as, 210from fungi, 143natural products as, 66, 102–103nionribosomal peptides as, 111

Biology, natural products in, viiBiomaterials, plant terpenoids as, 127

394 INDEX

Biosynthesis . See also Chiral synthesis;Coenzyme biosynthesis entries;Combinatorial biosynthesis; Fatty acidbiosynthesis; Glucan synthesis inhibitors;Macrotetrolide biosynthetic gene cluster;Photosynthesis; Polyketide biosynthesis;Porphyrin biosynthetic enzyme deficiencies;Retrobiosynthetic analysis; Solid-phasepeptide synthes (SPPS); Synthesis

of abietic acid, 137of ajmalicine and tetrahydroalstonine,

219–220of ajmaline, 216–219of alkaloids, 209, 210, 216, 220–221of antibiotics, 269, 270–274, 274–279,

279–281of archaeal coenzymes, 257of artemisinin, 134of bacitracin, 114of berberine, 213of β-carotene, 256of biotin, 253, 254of caffeine, 224–225, 225–226of chlorophylls, 257of coenzyme precursors, 258of cofactors/coenzymes, 239–240, 240–241,

245, 246, 257, 258, 259, 260, 261common steps in plant terpenoid, 130of diterpene resin acids, 136, 137of diterpenes, 131of erythromycin, 274, 276of farnesyl diphosphate, 130of flavin coenzymes, 258of flavocoenzymes, 245of folate, 245of geranyl diphosphate, 131of geranyl geranyl diphosphate, 131of GTP, 258of GTP-related coenzymes, 245of hemiterpenes, 131of hemiterpenoids, 130of human coenzymes, 260of iron/sulfur clusters, 242–243of isoprene, 130–132of isoprenoid cofactors, 253–256of isoquinoline alkaloids, 210–213of menthol, 132–133of methanopterin, 245of molybdopterin, 242, 245, 246, 260of monensins, 194, 195of monoterpenes, 131of monoterpenoids, 133of MOS, 153of morphine, 214–215, 220

of nanchangmycin, 199, 200of naphthopyrone, 150, 151, 152, 153of nicotinamide, 247–249of nonactin, 199, 200–202of nonribosomal peptides, 112, 114–118of orsellinic acid, 149of palmitine, 214of pantothenate, 249–251of plant alkaloids, 210of plant terpenoids, 127, 129–130, 131of polyether ladder compounds, 202–204of polyketide antibiotics, 272, 274of polyketide ethers, 189–207of purines, 245of pyridine nucleotides, 247–249, 250of pyridoxal phosphate, 247, 249of pyrroloquinoline quinone, 252–253regulation of antibiotic, 273–274of sanginarine, 213–214of scopolamine, 224of sesquiterpenes, 131of Taxol®, 135–136of terpene antibiotics, 276of terpenoid alkaloids, 216, 220–221of tetracyclines, 274of tetrahydrobiopterin, 241, 245, 246, 257, 260of tetrahydrofolate, 241, 245, 246of tetrapyrroles, 243–245of tetraterpenes, 158of thiamine pyrophosphate, 245–247, 248, 257of triterpenes, 131of tropane alkaloids, 222–224of vinblastine, 221of vindoline, 217–219, 220–221of vitamin B1, 241, 247of vitamin B2, 241, 245of vitamin B6, 247, 249of vitamin B12, 241–242, 257of vitamin C (ascorbic acid), 241, 251–252of vitamin D, 256, 262

Biosynthetic building blocks, of plant naturalproducts, 3. See also Building blocks

Biosynthetic engineering, of antibioticbiosynthesis, 279

Biosynthetic pathways. See also Acetatepathway; Coenzyme biosynthesis pathways;Convergent biosynthetic pathways; Fungalbiosynthetic pathways; Plant biosyntheticpathways; Prokaryotic biosyntheticpathways; Shikimate pathway

for alkaloids, 209, 210for antibiotics, 270for archaeal coenzymes, 257branched coenzyme, 257–258

INDEX 395

for coenzyme biosynthesis, 241–242, 242–260for coenzymes, 240–241HMGS-containing, 177, 179–180for isoprenes, 132for isoprenoid cofactor biosynthesis, 253–256

Biosynthetic precursors, coenzymes as, 257Biotechnology, cofactors/coenzymes in, 262Biotin, 240, 242, 243, 258

biosynthesis of, 253, 254as covalent coenzyme, 259

Biotin synthase, 253Bipolaris cynodontis, 92Bipolaroxin, 92Birch intermediates, in fungal polyketide

biosynthesis, 145Bisabolanes, 15, 16Bisabolene, 15, 17, 261,3-Bisphosphoglycerate (1,2-BPG), in antibiotic

biosynthesis, 272Bivalves, polyether poisoning of, 192–193Bizelesin, 79–80, 81Blackcurrant, 12b-lactams (β-lactams), 66–68, 291–292

in antibiotic biosynthesis, 277–278Blenoxane, 339Bleomycins, 78–79, 303, 304, 339, 340BMS-250749, 335Bohlmann, Jorg, ix, 127Boreostereum vibrans, 85Bornane, 12Borneol, 13, 14Bothrops jararaca, 309Botrytis cinerea, 90Branched coenzyme biosynthesis pathways,

257–258Brevenal, 202Brevetoxin B, 192Brevetoxins, 34, 190, 193, 202, 203Briarein A, 56, 57Briareum asbestinum, 56Britaxel-5, 332Brominated compounds, in marine natural

products, 32Bromotyrosine derivatives, in marine natural

products, 44Brookhaven Protein Data Bank, 259–260Brown algae, diterpenoids from, 56Bryostatin 1, 170Bryostatins, 41, 176, 181, 182, 305

HMGS-containing biosynthetic pathway for,177

Bryozoansindole alkaloids from, 51macrolides from, 38, 41

Buchholz, Tonia J., ix, 163Bugula neritina, 41, 305Building blocks. See also Biosynthetic building

blocks; Scaffoldsin antibiotic biosynthesis, 274, 275, 280in nonribosomal peptide synthesis, 112, 114,

115of terpenoids, 128

Bulgarane, 16Buprenorphine, 299–300Burkholderia, 164, 165Buruli ulcer, 164–165Butenyl-spinosyns, 101, 102

Cadinane, 16Caffeic acid, 20Caffeine biosynthesis, 224–225, 225–226

metabolic engineering of, 225–226Calcineurin, 98, 308Calicheamicin, 306, 307, 339–341Calyculin A, 42Calystegines, in tropane alkaloid biosynthesis,

224Camellia, 225Camphanes, 13, 14Camphene, 12, 13, 14Camphor, 13, 14Camphotheca acuminata, 301, 334, 355Camphotheca alkaloids, 352, 353, 355–357Camphothecin analogs, 334, 355–357Camphothecins (CPTs), 301, 302, 334, 354,

355–357Camptosar, 334, 356Canadine, 212

in berberine biosynthesis, 213Canadine transferase (CT), 211Cananga odorata, 8Cancer. See Anticancer agents; Antineoplastic

agents; Antitumoral entries; Antitumorcompounds

Candida, lipopeptides against, 76Candidatus, HMGS-containing biosynthetic

pathway of, 177Cangorosa, 362Cangorosin B, 362, 363Canola, 25Cantaurea maculosa, 90Capnella imbricata, 55Capnellane, 55, 56Captopril, 309, 310Caranes, 12, 13Carbamoylation, in antibiotic biosynthesis, 277Carbamoyltransferases, in antibiotic biosynthesis,

277

396 INDEX

Carbapenems, 67, 68, 292, 293Carbasugars, 94Carbohydrate-based inhibitors, 94Carbohydrates. See also Sugars

coenzymes from, 240–241in creating plant natural products, 4–6

Carbon atoms, atypical polyketide domains and,175–176

Carbon–carbon bonds, unsaturated, 167Carbonimidic dichloride group, 58Carboxylic acids

in antibiotic biosynthesis, 272coenzymes from, 240–241in pantothenate biosynthesis, 249, 251

Cardinane, 16Cardiovascular agents, 308–310. See also Heart

diseaseCarene, 12, 13Carlosic acid, 144, 147Carotenoids, 240, 262Carum carvi, 12Carvacrol, 11, 12Carveol, 11, 12Carvone, 11, 12Caryophyllane, 16Caspofungin, 77, 297, 298Cassia, 7Catalytic domains . See also Acetyltransferase

(AT) domains; Acyl carrier protein domain;Adenylation (A) domain; Chain-releasing(CR) domain; Claisen Cyclase (CLC)domain; Claisen-cyclase/thiolesterases(CLC/TE) domains; C-Met domains;Condensation (C) domain; Core domains;C-terminal docking domain; Cyclization(Cy) domain; Dehydratase (DH) domains;Enoyl CoA hydratase-like (ECG) domains;Enoyl reductase (ER) domain;Epimerization (E) domain; Essentialdomains; Formylation (F) domain; FUSS(fusarin synthetase) domains; GCN5-relatedN -acetyltransferase (GNAT) domain; KASdomains; Ketoreductase (KR) domains;Ketosynthase (KS) domain; KR-DH domainpair; KS domains; KSQ domain; Methyltransferase (Mt) domain; Methylation (Mt)domain; Modifying domains; N-methylation(Mt) domain; N-terminal docking domain;Optional domains; Oxidation/oxidase (Ox)domain; Oxygenase (Oxy) domain; Peptidylcarrier protein (PCP) domain;Phytanoyl-CoA dioxygenase (PhyH)domain; Product template (PT) domain;Pyrone synthase (PS) domain; R domains;

Reduction (R) domain; Starter unit loadingdomain (SAT); Sulfotransferase (ST)domains; Thioesterase (TE) domain; WASCLC domain

atypical, 175–182in nonribosomal peptide synthesis, 112,

114–118Catecholamine type neurotransmitter deficiency,

260Caterpillars, 376Catharanthine, 219

in vinblastine biosynthesis, 221Catharanthus alkaloids, 352, 353–354Catharanthus roseus, 26, 216, 219–220, 221,

222, 301, 327, 353Cathenamine, 217, 218, 219–220

in terpenoid indole alkaloid biosynthesis, 216Cations, metals as, 190–191Caulerpenyne, 55CC-1605, 79–80CCK receptor binding screening assays, 312Cefuroxime, 67Cell-based bioassay methods, 352Cell cycle, cancer and, 326. See also MitosisCells, plant terpenoids from, 128Cell types, in terpenoid alkaloid biosynthesis,

220–221Cellular topology, in eukaryote coenzyme

biosynthesis, 259Cellulose, 5, 6Cemranes, 17, 18Cephalexin, 292Cephalodiscus grichristii, 54Cephalosporin C, 271, 278, 292Cephalosporins, 67, 292Cephalosporium, 91Cephalosporium acremonium, 292Cephalostatins, 54Cephalotaxine, 358, 359Cephalotaxus, 358Cephalotaxus alkaloids, 358–359Cephalotaxus fortunei, 358Cephalotaxus harringtonia, 358Cephalothin, 67Cerivastatin, 309, 310CGP41251, 303, 304Chain, Ernst B., 291Chain extension component, 150, 152, 154Chain length determination, counting mechanism

in, 154Chain-releasing (CR) domain, for

nanchangmycin, 198–200Chalcone synthase (CHS), 26Chamaecyparis nootkatensis, 12

INDEX 397

Chaminic acid, 12, 13Checkpoint kinases, as anticancer agent targets,

326–327Cheilanthifoline, 212Chemistry. See also Atmospheric chemistry;

Combinatorial chemistry; Marine naturalproducts chemistry; Regiochemistry;Stereochemistry

of antibiotic biosynthesis, 274–279natural products in, viiof polyketide ethers, 194–204of terpenoids, 129–136, 137

Chemoenzymatic approaches, for producingnovel peptides, 120–122

Chemoinformatics, antibiotics and, 270Chinese civilization

folkloric medicine in, 376plant preparations in, 289, 351, 352

Chiral synthesis, in studying terpenoids, 138Chivosazol. 172Chloroamphenicol, 293, 294Chloro-indolocarnazoles, 276Chlorolissoclimide, 57Chloronicotine, 300Chlorophylls, 17, 243, 244, 253, 256

biosynthesis of, 257Chloroquine, 298Chlortetracycline, 276, 293, 294Cholecalciferol, 255, 256Cholesterol, 309Cholesterol levels, 144Chondrillin, 33Chondrodendron tomentosum, 25, 290Chorismate, 245Chromatography, in studying terpenoids, 138Chromobacterium violaceum, 67Chromopeptide antibiotics, 78Chrysanthemic acid, 9, 10Chrysanthemum cinerariaefolium, 9Chrysophanol-anthrone, 6–7Chymostatin, 86Ciguatoxins (CTXs), 34, 35, 193, 202Cinachyrolide, 39Cinchona bark, 297Cinnamaldehyde, 21Cinnamic acid, 20Cinnamic acid derivatives, 20, 21–22Cinnamomum camphorum, 13Cinnamomum zeylanicum, 12, 21Cinnamon, 12, 21Ciocalypta, 57Ciomomonas testosteroni, 196Ciona savignyi, 51

cis double bonds, in polyketides, 169–173,173–174, 182

Citranellal, 9Citranellol, 9Citreoisocoumarin, 152Citrinin, 143, 144, 147, 150, 151, 152, 153Citrus, 11Citrus aurantium, 11, 14Citrus bergamia, 15Citrus junos, 15Citrus reticulata, 11, 14Citrus sinensis, 13, 14Citrus vulgaris, 9Civjan, Natanya, viiClaisen condensation

in antibiotic biosynthesis, 274in isoprenoid cofactor biosynthesis, 256

Claisen Cyclase (CLC) domain, for NR-PKS,153

Claisen-cyclase/thiolesterases, 152, 154Claisen-cyclase/thiolesterases (CLC/TE)

domains, for NR-PKS, 152–153Clavelina, 50Clavelina moluccensis, 54Clavelina picta, 54Clavepictine B, 53–54Clavulanic acid, 67–68Clavulinic acid, 293Clinically relevant polyketide drugs, 164Cliona, 50Clitopilus scyphoides, 271Cloning

in antibiotic biosynthesis research, 279in plant alkaloid biosynthesis, 210in studying terpenoids, 138

Clorobiocin, 277C-Met domains, for NR-PKS, 153C-methyl transferases (C-MeT), 152, 153, 155Cnidarians, terpenoids from, 55CNMT (coclaurine N -methyl transferase), 211CO2 (carbon dioxide)

in archaeal coenzyme biosynthesis, 257coenzymes from, 240–241

CoA thiolesters, in fungal polyketidebiosynthesis, 144–145

Coban®, 191Cocaine, 23, 24, 222, 223Coccidiosis, 191Cocculus antitumor agents, 362Cocculus trilobus, 362Cochliobolus heterostrophus, 148Coclaurine, 213Codeine, 210, 212, 299, 300

in morphine biosynthesis, 215

398 INDEX

Codeinone, 212in morphine biosynthesis, 215

Coelichelin, 113, 116Coenzyme A (CoA), 165, 240

nonactin and, 201, 202in pantothenate biosynthesis, 250, 251

Coenzyme B12, 240, 244in vitamin B12 biosynthesis, 241–242

Coenzyme biosynthesis, genetic deficiency in,260–261

Coenzyme biosynthesis enzymesas anti-infective drug targets, 261three-dimensional structures of, 259–260

Coenzyme biosynthesis pathways, druginteraction with, 261–262

Coenzyme F420, 246Coenzyme F430, 244

in archaeal coenzyme biosynthesis, 257Coenzyme Q10, 240, 256, 262Coenzyme Q family, 253Coenzymes, 239. See also Archaeal coenzymes;

Cofactorsin biosynthesis of their own precursors, 258as biosynthetic precursors, 257covalent, 258–259origins of human, 240

Cofactors, 239–267. See also Coenzymesbiosynthetic pathways of specific, 242–260in biotechnology, 262diversity and functions of, 239–240general aspects of, 240–242medical aspects of, 260–262

Coffea, 225, 226Coffee beans, genetically engineered, 225–226Coffee plants, 225Colchicine, 24, 25, 359, 360

isolation of, 290Colchicine derivatives, 359, 360Colchicum alkaloids, 359, 360Colchicum autumnale, 25, 359Colchinoids, 359, 360Coleophoma empetri, 77, 297Colletotrichum lagenarium, 148, 152Combinatorial biosynthesis, 279Combinatorial chemistry, 342–343Combretastatin A4, 326Combretastatin A4 phosphate, 302–303, 329Combretastatins, 328, 329Combretum caffrum, 302, 328Commiphora abyssinica, 15Compactin, 143, 147, 309Complexity, of fungal polyketides, 148Condensation, in nonribosomal peptide synthesis,

112

Condensation (C) domain, 156exchange of, 119, 120in nonribosomal peptide synthesis, 112, 114,

115, 116–117, 118NRPS module, 158

Conifersditerpene resin acids from, 136, 137plant terpenoids from, 128

Coniferyl alcohol, 21Conotoxins, 43, 300Convergent biosynthetic pathways, for coenzyme

biosynthesis, 241Copalyl diphosphate, in diterpene resin acid

biosynthesis, 136, 137COPE rearrangement, 15Coptis japonica, 210, 212, 213Corals, diterpenoids from, 56–57Cordycepeptide A, 376, 377Cordycepin, 102, 376, 377Cordyceps militaris, 102Cordyceps sinensis, in folkloric medicine, 376,

377Cordyols, 376, 377Core domains, 165–166

in antibiotic biosynthesis, 278for PR-PKS, 154, 156

Coriandrum sativum, 12Corrinoids, 243

in vitamin B12 biosynthesis, 242Corticatic acid, 33, 34Corynanthe, 217Coumaric acid, 20, 22Coumarin derivatives, 365–367Coumarins, 22, 234-Coumaroyl-CoA, 26Coumaryl alcohol, 21Counting mechanism, in chain length

determination, 154Covalent attachment, in nonribosomal peptide

synthesis, 112Covalent coenzymes, 258–259Cox, Russell J., ix, 143Crambe crambe, 52Crataegus, 22Crixivan®, 299Crohn’s disease, 96Crotonase fold family, 178Cryptothera crypta, 31Crystallographic substrate tapping, in antibiotic

biosynthesis research, 281C-terminal docking domain, 166Curacin, 168, 178–181, 182

HMGS-containing biosynthetic pathway for,177

INDEX 399

Curacin A, 170, 173–174, 175, 176Curare, 25, 290Curcuma, 363–365Curcuma aromaica, 365Curcumin, 364Curcumin analogs, 364–365Curcuminoids, 364Curcumol, 364curG gene, 173CurM module, 174Cyanobacteria, 91

marine natural products from, 32Cyanosafracin B, 341, 342Cyclic peptides, in marine natural products, 44,

46Cyclic peroxides, 33Cyclin-dependent kinases (CDKs), 352Cyclization, in nonribosomal peptide synthesis,

112Cyclization (Cy) domain, 179–180

in nonribosomal peptide synthesis, 112, 118Cyclization reactions, of monoterpene precursors,

9Cycloartane, 18, 19Cyclodercitin, 49Cyclofarnesanes, 14–15, 16Cyclohexane monoterpenoids, 10–12Cyclononylprodigiosin, 99–100Cyclopentane monoterpenoids, 10Cyclo-prodigioson, 99Cyclosporin/cyclosporine, 98, 112Cyclosporin A/cyclosporine A, 96, 307,

308Cyclostellettamine, 47Cymene, 11, 12Cynodon dactylon, 87Cyperus microiria, 91Cysteine, 242

iron/sulfur clusters and, 243in pantothenate biosynthesis, 250

Cytisus scoparius, 24Cytochrome P450 monooxygenases, 129, 134,

276, 277in morphine biosynthesis, 215in Taxol® biosynthesis, 135

Cytoplasm, coenzyme biosynthesis in,259

Cytostatic agents, coenzyme biosynthesisenzymes as targets for, 261

Cytotoxicityantineoplastic agents and, 306defined, 352

Cytotoxic metabolites, in marine naturalproducts, 32

Dactinomycin, 303, 304, 339Dalbergia odorifera, 360Dalesconols, 98, 99Dalfopristin, 294, 296Dammarane, 18, 19Daptomycin, 113, 121, 122, 271, 272, 274, 294,

295Databases, in studying terpenoids, 138Daunorubicin, 81, 82, 336, 337DCK, 365–367DCP, 366–36710-Deacetylbaccatin III, 354, 355Deacetylcephalosporin C, 278Deacetylvindoline, 219Deazaflavin-type coenzymes, 245Decaffeinated coffee, 225–226Decalins, 143, 147Decarboxylation, 174Decarestrictine, 143, 147Degradation, in self-protection against

antibiotics, 274Dehydratase, in fungal polyketide biosynthesis,

146, 154, 155Dehydratase (DH) domains, 179–180. See also

KR-DH domain pairin fungal polyketide biosynthesis, 154, 155polyketide double bonds and, 167, 169, 171,

172, 176Dehydration, in fungal polyketide biosynthesis,

146Dehydrocurvularin, 143, 147Dehydrodidemnin B, 46, 47Dehydrogeissoschizine, 217, 218Dehydroreticuline, in morphine biosynthesis, 214Dehydroreticulinium ion, 212Dehydrovinblastine, in vinblastine biosynthesis,

221Demethylmonensins, 197Demethylsuberosin, 22, 23Dencichine, 373Dendrodoa grossulatia, 51Denrolasin, 14, 151-Deoxy-D-xylulose phosphate

in pyridoxal phosphate biosynthesis, 247, 2496-Deoxyerythronolide, 2726-Deoxyerythronolide B synthase, 165Deoxy-frenolicin, 88–89Deoxyherqueinone, 143, 14710-Deoxymethylnolide, 166Deoxynucleotidetriphosphate (dNTP)

in antibiotic biosynthesis, 272, 2737-Deoxystaurosporine, 303, 304Deoxysugar nucleotidyldiphosphates (dNDP), in

antibiotic biosynthesis, 275–276, 278

400 INDEX

Deoxytedanolides, 40, 41, 42Depsipeptides, 46, 47Dercitin, 49Dercitus, 49Desacetoxyvindoline, 219Desacetylvindoline, in vindoline biosynthesis,

220Destruxins, 100, 101Dethiobiotin, in biotin biosynthesis, 253, 254D-hydroxyl group configurations, polyketide

double bonds and, 169Diabetes, 94, 95Diarrhetic shellfish poisoning (DSP), 35–36,

192, 193Diazona angulata, 52Diazonamide A, 51–52Dibromophakelin, 48Dictyodendrilla verongiformis, 50Dictyodendrins, 50Dictyota crenulata, 56Dictyotadial, 56Dictyota linearis, 56Didemnaketal C, 59Didemnanaketal B, 59Didemnin B, 46, 47Didemnum, 49, 59Didemnum proliferum, 43Diels-Alder reaction, 156Difficidin, 170, 176

HMGS-containing biosynthetic pathway for,177

Digitalis glycosides, 290Digitalis lanata, 290Digitalis purpurea, 20Digitoxin, 19, 20, 290Dihydroartemisinin, 370Dihydrofolate, 240Dihydroisocangorosin A, 362, 363Dihydromonacolin L, 155, 156Dihydroneopterin, 246, 258Dihydroneopterin triphosphate, 246, 257Dihydroquinoline alkaloids, 53Dihydrosanginarine, 212

in sanginarine biosynthesis, 2141,2-Dihydrovomilenine, 218Dihydroxyacetone phosphate

in pyridine nucleotide biosynthesis, 249, 250in pyridoxal phosphate biosynthesis, 247, 249

7,20-Diisocyanoadocaine, 57–58Dimethylallyl diphosphate (DMAPP), 7, 8, 22

isoprene from, 130in isoprenoid cofactor biosynthesis, 253–256as plant terpenoid precusros, 130

(R)-3,7-dimethyloctanol, 9

Dimethylorsellinic acid, 1443,5-Dimethylorsellinic acid, 153Dimethyl succinyl betulinic acid (DSB),

368–369Dinactin, 190, 201Dinoflagellates, 32

guanidine alkaloids from, 52macrolides from, 38open-chain polyketides from, 36–38polyethers from, 34–36toxic marine polyethers from, 192–193

Dinophysis, 35, 36Dinophysis acuminata, 192Dinophysis fortii, 192Dioxane, 33Dioxoloane, 33Dioxygenases, in antibiotic biosynthesis, 277Disaccharides, 5Discodermia calyx, 42Discodermia dissoluta, 37, 305Discodermolide, 37–38, 305–306Discorhabdin C, 49–50Disorazole A1, 170, 172, 173Diterpene resin acids, 127, 130, 136, 137

biosynthesis of, 136, 137Diterpenes, biosynthesis of, 131Diterpene synthases, 26Diterpenoids

diterpene resin acids as, 136in marine natural products, 56–57Taxol® as, 134–136

Diterpenoids, 17, 18, 95, 128, 360, 365, 366DNA (deoxyribonucleic acid)

compounds targeting/interacting with, 325,326, 338–341

and PKS genes in fungi, 148–149topoisomerases and, 327

DNA sequence analysis, 175Docetaxel, 331, 332, 354, 355Docosohexaenoic acid (DHA), 25DOD (7,10-dihydroxy-8(E)-octadecenoic acid),

95Dolabella auricularia, 44, 46, 305, 329Dolabellanes, 56Dolastatins, 44–45, 46, 305, 306, 329–331Domain exchange, in producing novel peptides,

119. See also Catalytic domainsDomoic acid, 43–44DOPA decarboxylase, 211. See also

L-dihydroxyphenylalanine (L-DOPA)Dopamine, 211

in isoquinoline alkaloid biosynthesis, 210–213Doratomyces putredinis, 87Dothistromin, 152

INDEX 401

Double-bond configuration, 163, 167Doxorubicin, 81, 82, 303, 304, 336, 337, 342Doxycycline, 294Dragmacidin, 51Dragmacidon, 51Drinabe, 16Drug discovery

future of, 376–377among plant-derived natural products,

351–388Drugs

derived from microbial fermentations,290–291

natural products as, 289, 325–326, 342–343Duboisia, 222Dysidea avara, 56Dysidea etheria, 55, 58Dysidea herbacea, 43, 55Dysidiolide, 58Dysiherbaine, 43–44Dysinosin A, 45

EC145 R, 353, 354ECH groups, 178–181

jn HMGS architecture, 181–182Echinocandin B, 271Echinocandins, 76–77, 297Echinochalina bargibanti, 32Ecosystems, roles of plants in, 4Ecteinascidia turbinata, 53, 306, 341Ecteinascidin-743, 305, 306Ecteinascidins, 53, 54, 341–342Efflux, in self-protection against antibiotics, 274Efflux pumps, in antibiotic biosynthesis, 278Egyptian civilization, plant preparations in, 289Eicosapentaenoic acid (EPA), 25Eimeria, 191, 312Eisai Research Institute, 329Eisenreich, Wolfgang, ix, 239Elatol, 55Eldisine, 353, 354Electron diffraction studies, of paclitaxel, 332Electrospray ionization Fourier Transform mass

spectrometry (ESI-FTMS), in antibioticbiosynthesis research, 281

Elemanes, 15, 16Elemenone, 15, 17Eleutherobia, 57Eleutherobin, 57Eleutherococcus senticosus, 371, 373–374Eleutherosides, 374Elongation modules, 165, 167, 172, 173,

174–175Elysia rufescens, 46

Emarginatines, 362, 363Emodin, 7, 26Emodin-anthrone, 6–7Enalapril, 309, 310Enamides, 41Enantiomeric separation, in studying terpenoids,

138Enediynes, in marine natural products, 43Enoyl CoA hydratase-like (ECG) domains, 176Enoyl reductase (ER) domain, 166, 168, 176,

179–180. See also Enoyl reduction (ER)Enoyl reduction (ER), in fungal polyketide

biosynthesis, 146, 155, 156–157. See alsoEnoyl reductase (ER) domain

Enterobactin, 117Enzymatic assays, in antibiotic biosynthesis

research, 280–281Enzyme-bound substrates, in antibiotic

biosynthesis research, 281Enzyme-catalyzed synthesis, of antibiotics, 270Enzyme deficiencies, 260–261Enzyme inhibitors

applications of, 84–85carbohydrate-based, 94among microbial natural products, 84–8

Enzymes. See also Apoenzymes; Archaealcoenzymes; Catalytic domains; Coenzymeentries; Cofactors; Fab enzymes; Synthases;Synthetases

in ajmaline biosynthesis, 216–219in antibiotic biosynthesis, 270, 274–279in berberine biosynthesis, 213in caffeine biosynthesis, 225for coenzyme biosynthesis, 239–240in isoquinoline alkaloid biosynthesis, 210–213in menthol biosynthesis, 133in modular PKSs, 165in morphine biosynthesis, 214–215in plant alkaloid biosynthesis, 210in terpenoid indole alkaloid biosynthesis, 216in terpenoid indole alkaloid metabolic

engineering, 221–222in tropane alkaloid biosynthesis, 222–224in vinblastine biosynthesis, 221in vindoline biosynthesis, 220–221in vitamin C biosynthesis, 251–252

Enzymologyof antibiotic biosynthesis, 274–279in fungal polyketide biosynthesis, 146–148

Ephedra sinaica, 309Ephedrine, 309, 310Epibatidine, 300Epidermal cells, plant terpenoids from, 128

402 INDEX

Epidermis, in terpenoid alkaloid biosynthesis,221

Epimerization, in nonribosomal peptidesynthesis, 112

Epimerization (E) domain, in nonribosomalpeptide synthesis, 112, 114, 117–118

epi -monensins, 195, 197Epipedobates tricolor, 300Epipodophyllotoxins, 354, 355Epirubicin, 336epi -vellosamine, 218

in ajmaline biosynthesis, 216–218Epothilone B, 164Epothilone D, 170, 172Epothilones, 81, 112, 118, 172, 303–304,

332–333Epoxidation, 158, 202–204

in antibiotic biosynthesis, 276Equisetin, 155, 158, 159Eremophilane, 16Ergosterol derivatives, 376, 377Eribulin, 328–329, 330Erythroascorbic acid, in vitamin C biosynthesis,

251–252Erythromycin, 68, 69, 89, 271, 272, 293–294,

295biosynthesis of, 274, 276

Erythromycin A, 164building blocks and scaffold for, 275

Erythronolide, 272Erythroxylon coca, 23Escherichia coli, 134, 178, 212, 213, 216, 247,

298β-lactams effective against, 68

Eschscholzia californica, 210Essential domains, in nonribosomal peptide

synthesis, 112, 114–117Esters, of fatty acids, 6Ethers, polyketide, 189–207Ethylmalonate, in antibiotic biosynthesis, 274Etopophos, 336, 357, 358Etoposide, 302, 303, 336, 337, 357, 358Eubacteria, 257

coenzymes from, 240–241tetrapyrrole biosynthesis and, 243thiamine pyrophosphate biosynthesis in, 247

Eucalyptus, 12Eucalyptus globulus, 13Eucalyptus phellandra, 11Eudesmane, 16Eudistoma, 49Eudistoma olivaceum, 51Eudistomins, 51Eudistone A, 49

Eugenol, 22Eukaryotes, 257

coenzyme biosynthesis in, 259Euphorbia diterpenoids, 365, 366Euphorbia ebrateolata, 365Euphorbia kansui, 365Europe, herbal remedies in, 351–352European Union, 305Eusynstyela latericius, 49Expressed sequence tags (ESTs), 129, 130Extended sesquiterpenes, 56Extender units

in conventional modular type I PKS, 166polyketide diversification and, 175

Extraction, in studying terpenoids, 136–138

Fab enzymes, 313Factor F0, in archaeal coenzyme biosynthesis,

257FAD, 240

as covalent coenzyme, 258Farnesane, 14, 16Farnesenes, 14, 15Farnesol, 14, 15Farnesyl diphosphate (FPP), 14

in artemisinin biosynthesis, 134biosynthesis of, 130

Farnesyl diphosphate synthase (FPPS), 26Fatty acid biosynthesis . See also Fatty acid

synthesis entriesassembly cycle in, 145–146fungal polyketide biosynthesis and, 145

Fatty acid derivatives, in marine naturalproducts, 32–33

Fatty acids, 6, 25, 95in antibiotic biosynthesis, 274–275

Fatty acid synthase (FAS), 95fungal polyketide biosynthesis and, 146–148,

149, 151, 154Fatty acid synthesis, polyketide diversification

and, 175Fatty acid synthesis inhibitors, 313Feeding studies. See Isotopic feeding

experimentsFenchanes, 13–14Fenchone, 12, 13–14Fermentation, 262. See also Microbial

fermenationsfungal polyketide biosynthesis and, 145

Ferula, 22Ferulic acid, 20Filamentous fungi, natural products from, 65–66Filipin, 76Fin-fish poisoning, 193

INDEX 403

Fingolimod, 97Fischer, Markus, ix, 239Fishes, marine natural products from, 32Fish poisoning, 193FK506, 307–308FKBP-12 (FK-binding protein 12), 98Flavin coenzymes, biosynthesis of, 258Flavocoenzymes

biosynthesis of, 245iron/sulfur clusters and, 242–243

Flavonoids, 22, 23, 26Fleming, Alexander, 269, 291Florey, Howard, 291Flowers, plant terpenoids from, 128Fludelone, 333Fluvastin, 309, 310FMN, 240, 257

as covalent coenzyme, 258FMN-dependent monooxygenases, in antibiotic

biosynthesis, 276Fmoc protective group strategy, 120Foeniculumvulgare, 14, 22Folate, 240. See also Folic acid

biosynthesis of, 245Folic acid, 242, 353, 354Folkloric medicine, active compounds isolated

from, 369–376Food and Drug Administration (FDA), U.S. 301,

328, 341Formylation, in nonribosomal peptide synthesis,

112Formylation (F) domain, in nonribosomal peptide

synthesis, 112, 118Formyltetrahydrofolate, 118Forskolin, 17, 18Fosmidomycin, 261Fourier Transform methods, in fungal polyketide

biosynthesis, 145FR901379, 76–77, 297Fragranol, 9, 10Friedelane, 18, 19Friulimicin, 274Fructose, 5Fumonisin B1, 155Fumonisins, 144, 147Functional genomics approaches, to studying

plant terpenoids, 129–130Fungal biosynthetic pathways, for alkaloids, 210Fungal HR-PKS, 155–159Fungal HR-PKS genes, 149, 152Fungal NR-PKS, 149–153, 159Fungal NR-PKS genes, 149–153Fungal PKS genes, classes of, 149Fungal polyketides, 143–161

biological properties of, 144biosynthesis of, 144–148, 149, 150–157diversity and functionalities of, 143–144molecular structures of, 147topics for future research on, 159

Fungal polyketide synthases, 148–149Fungal PR-PKS, 154, 156, 159Fungal PR-PKS genes, 149Fungi

antibiotic biosynthesis among, 270–271antibiotics from, 269, 270antitumoral steroid alkaloids from, 79, 80β-lactams from, 66–67caterpillars and, 376coenzymes from, 240–241enzyme inhibitors from, 87–89in folkloric medicine, 374–376insecticide peptides from, 100, 101linking PKS genes and compounds in,

148–149marine natural products from, 32medically and agriculturally important

antibiotics produced by, 271natural products from, 65–66, 291polyketides in, 143–161

Furanocoumarins, 22, 23Furanosesquiterpenes, 55Furodysinin, 55, 56Fusarin C, 144, 147, 148, 155, 158Fusarium, 91Fusarium heterosporum, 159Fusarium monilliforme, 158Fusarium pallidoroseum, 312Fusarium venenatum, 158Fusetani, Nobuhiro, ix, 31FUSS (fusarin synthetase) domains, 155, 156,

158, 159

Galactose, 5in vitamin C biosynthesis, 252

Galantamine, 301Galanthus nivalis, 301Galium odoratum, 10Gallic acid, 20Gallotannins, 20Gamberiol, 202Gambierdiscus, 193Gambierdiscus toxicus, 34, 193Gambieric acids, 34, 35, 190, 193, 202Ganoderic acids, 375, 376Ganoderiol, 375Ganoderma lucidum, in folkloric medicine,

374–376Ganodermanondiol, 375

404 INDEX

Ganodermanontriol, 375Gas chromatography, in studying terpenoids, 138Gastrointestinal-active macrolides, 89Gastrointestinal motor stimulators, among

microbial natural products, 89GCN5-related N -acetyltransferase (GNAT)

domain, 179–180Geldanamycin, 277, 336, 338Gene clusters

in antibiotic biosynthesis, 277, 278–279for marine polyethers, 204–205for monensins, 194, 196for nanchangmycin, 197–200for nonactin, 201in pyrroloquinoline quinone biosynthesis,

252–253Gene-fishing expeditions, 158Genes

in antibiotic biosynthesis, 274, 278–279encoding terpenoid synthases, 129in isoquinoline alkaloid biosynthesis, 213in morphine biosynthesis, 215in plant alkaloid biosynthesis, 210in studying terpenoids, 138in Taxol® biosynthesis, 135

Genetic defects, in human coenzymebiosyntheses, 260

Genetics, of antibiotic biosynthesis, 274,278–279

Genistein, 22, 23, 88Genome sequences, in studying terpenoids, 138Genome sequencing, of antibiotic-producing

organisms, 270Genomics approaches, to studying plant

terpenoids, 129–130Geranial, 9Geraniol, 9Geranyl diphosphate (GPP)

biosynthesis of, 130in menthol biosynthesis, 133

Geranyl geranyl diphosphate (GGPP)biosynthesis of, 130in diterpene resin acid biosynthesis, 136, 137in Taxol® biosynthesis, 135

Germacranes, 15, 16Germacrenes, 15, 17Ginsengs, in folkloric medicine, 370–374Ginsenosides, 371–372, 372–373Girolline, 44Glandular trichomes

menthol from, 132plant terpenoids from, 128

Glarea lozoyensis, 76, 77, 297Glucan synthesis inhibitors, 297

Gluconobacter oxydans, 94Glucose-1-phosphate, in vitamin C biosynthesis,

252Glucose, 5Glucose 6-phosphate, in vitamin C biosynthesis,

252α-Glucosidase inhibition, 94Glucuronate, in vitamin C biosynthesis, 252Glutamate, in pyrroloquinoline quinone

biosynthesis, 252–253Glutamyl-tRNA, 244Glycerate, in antibiotic biosynthesis, 274Glycerol, 6Glycine, 244Glycoceramides, 33Glycopeptide family, 303Glycosides, 5Glycosylation, in antibiotic biosynthesis, 276,

278Glycosyltransferases, in antibiotic biosynthesis,

277, 278Glycyrrhizic acid, 19, 20Golden Age of antibiotics, 291Gonyaulax, 193Gorgonians, diterpenoids from, 56–57G-proteins, 262Gracilin B, 56, 57Gramicidins, 73, 74, 112, 113, 116–117, 118Gramicidin synthetase, 115Gram-negative pathogens, 293Gram-positive bacteria, 294

ansamycins effective against, 70peptide antibiotics against, 71–73, 74

Greece, plant preparations in, 290Griseofulvin, 144, 147Grossularine, 51GTP cyclohydrolases, 245. See also Guanosine

triphosphate (GTP)Guaiane, 16Guanidine alkaloids, in marine natural products,

47, 52Guanosine triphosphate (GTP)

biosynthesis of, 258coenzyme family biosynthesized from, 245,

246Gulonate, in vitamin C biosynthesis, 252Gulonolactone, in vitamin C biosynthesis,

252Gunatilaka, A. Leslie, ix, 3Guzman-Trampe, Silvia, ix, 65Gymnangiamide, 44, 45Gymnangium regae, 44Gymnodinium breve, 34, 193Gymnodinium catenatum, 52

INDEX 405

Haase, Ilka, ix, 239Haemophilus, β-lactams effective against, 68Haemophilus influenza, antibiotics against, 70Hahella chejuensis, 80, 99Halenaquinols, 43Halenaquinones, 43Halichondria okadai, 35, 39Halichondrin B, 329, 330Halichondrins, 39, 40Haliclona, 41, 47, 48, 59Halicyclamine, 47, 48Halitoxin, 47Halogenases, in antibiotic biosynthesis, 277Halogenated compounds, in marine natural

products, 32Halogenated terpenoids, 55Halogen-containing antibiotics, 276Hamel group, 329Hamycin, 76Harringtonine, 358, 359Headspace sampling, in studying terpenoids,

136–138Heart disease, 144. See also Cardiovascular

agentsHeat shock protein (Hsp90), as anticancer agent

target, 327Heliotropium, 22Hemes, 243, 244, 255, 256Hemiasterlin, 306, 307Hemichordates, steroidal alkaloids from, 54Hemiterpenes, 7, 8

biosynthesis of, 131isoprene as, 130–132

Hemiterpenoids, 8, 128biosynthesis of, 130

Hepialus armoricans, 376Heptaprenoids, 59Herbal remedies, history of, 351–352Herbicidal lactones, 91Herbicidal macrolides, 91–92Herbicidal peptides, 90Herbicidal terpenes, 92Herbicides, among microbial natural products,

90–92Herbimycin, 91–92Heroin, 215Heterotrophic organisms, coenzyme biosynthesis

in, 240–241Hexabranchus, 39Hexanoyl CoA, 151Hexoses, 5Highly reduced (HR) compounds, 149High performance liquid chromatography–mass

spectrometry (HPLC-MS), 205

Hill, Alison M., ix, 189Histidine, in thiamine pyrophosphate

biosynthesis, 247, 248Histone deacetylase (HDAC), 313Histoplasma, lipopeptides against, 76HIV (human immunodeficiency virus), 365HMG CoA reductase inhbitors, 308–309HMG-CoA synthase (HMGS) cassettes,

170–171, 176architecture of, 181–182biochemistry of, 176–181functions of, 176reaction scheme of, 178

HOD (10-hydroxy-8(E)-octadecenoic acid), 95Homoharringtonine, 358, 359Homononactate, 199, 201Homoserine, 155, 158Hopane, 18, 19Horseradish peroxidase, vinblastine biosynthesis

and, 221HTI-286, 306, 307Humans, origins of coenzymes in, 240Humulanes, 15, 16Humulenes, 15, 17Humulol, 15, 17Humulus lupulus, 8, 9Hybrid antibiotics, 279Hycamptin, 334, 356Hydroids, peptides from, 44, 45Hydroxyakalone, 87Hydroxyanthranilic acid, in pyridine nucleotide

biosynthesis, 247–249, 2503-Hydroxybenzoic acid, 2010-Hydroxycamphothecin, 355, 3563-Hydroxyl-3-methylglutaryl-CoA, 178Hydroxylation, in antibiotic biosynthesis, 276Hydroxylation genes, for monensin, 1956-Hydroxymanzamine, 79, 80Hydroxymethylbilane, 244p-Hydroxyphenylacetaldehyde, 211

in isoquinoline alkaloid biosynthesis, 210–2134-Hydroxyphenylpyruvate, 245

in archaeal coenzyme biosynthesis, 2576-Hydroxyprotopine, 212Hydroxytabersonine, 219, 220Hydroxyvalidamine, 94Hyoscyamine, 23, 222, 223, 224

in tropane alkaloid biosynthesis, 224Hyoscyamus, 222Hyoscyamus niger, 224Hyperglycemia, 94Hypericin, 7, 26Hypericum perforatum, 7, 26

406 INDEX

Hypocholesterolemics, among microbial naturalproducts, 92–93

Hypoglycemic peptides, 95Hypoglycemics, among microbial natural

products, 94–95Hyrtiostatins, 39–40

Ianthella basta, 44Iboga, 217Idarubicin, 336Illicium varum, 22Iminium intermediate, in vinblastine

biosynthesis, 221Imipenem, 67, 68, 292, 293Imium dimer, 219Immunophilins, 308Immunosuppressant agents, 307–308

among microbial natural products, 96–100Immunosuppressive macrolides, 97–98, 99Immunosuppressive peptides, 96Immunosuppressive pyrrole compounds, 98–100Indian civilization, plant preparations in, 289Indinavir, 299Indole, 217Indole alkaloids, in marine natural products, 47,

51–52Indolizidine alkaloids, 24Indolizidines, in marine natural products, 53–54Indolocarbazoles, 334Indonesian medicine, 351Industrial production, of antibiotics, 273Ingenol diterpenoids, 365, 366Inorganic substrates, in antibiotic biosynthesis,

272Insecticide macrolides, 100–102Insecticide peptides, 100, 101Insecticides

among microbial natural products, 100–102nucleoside analogs as, 102

Intermediates, in antibiotic biosynthesis research,281

Invertebrates, natural products isolated frommarine, 31–64

Ionophoresmacrotetrolides as, 200metal complexes with, 190–191monensins as, 194polyketide polyethers as, 190–192selectivites of, 191

Ipomoea batatus, 14Ircinia variabilis, 58Iridoids, 10Irinotecan, 301, 302, 334, 356Iron/sulfur (Fe/S) clusters, 240

biosynthesis of, 242–243functions of, 242–243

Isaria sinclairii, 97IscU protein, iron/sulfur clusters and, 243Islandicin, 143, 147Isoagatholactone, 56Isoborneol, 13, 14Isocamphanes, 12, 13, 14Isocoumarin, 150, 152, 153Isocyanide, 58Isocyanide-containing natural products, 57–58Isocyanopupukeanane, 57Isocyanoterpenes, in marine natural products,

57–58Isoflavonoids, 22, 23Isolation, in studying terpenoids, 136–138Isopentenyl diphosphate (IPP), 7, 8, 257

in antibiotic biosynthesis, 276in isoprenoid cofactor biosynthesis, 253–256as plant terpenoid precursors, 130

Isopiperitenone, in menthol biosynthesis, 133Isopiperutenol, in menthol biosynthesis, 133Isoprene, 8, 127

biosynthesis of, 130–132Isoprene biosynthesis pathway, 132Isoprene synthases, 130, 132Isoprenoid cofactors, biosynthesis of, 253–256Isoprenoid pathways, 241Isoprenylated polyamines, 53Isoprenyl diphosphates, 130Isopulegol, 11, 12Isopulegone, 11, 12

in menthol biosynthesis, 133Isoquinoline alkaloids, 209, 210–215

molecular structures and applications ofrepresentative, 211–212

Isoquinolines, in marine natural products, 53Isotingenone, 362, 363Isotopic feeding experiments, 153, 156, 173–174

in antibiotic biosynthesis research, 279–280concerning monensins, 194concerning nonactin, 200

Isovaleric acid, 10ISP-1, 97Isu protein, iron/sulfur clusters and, 243Itokawa, Hideji, x, 351Ivermectin, 83, 271, 311Ixabepilone, 333

Jamaicamide, 170, 176, 182HMGS-containing biosynthetic pathway for,

177Jamu, 351Japanese–Chinese medicine, 351

INDEX 407

Japanese ginseng, 371Jasminium multiflorum, 10Jasmolactone, 10Jaspis, 42Jimenez-Estrada, Manuel, x, 65J-K ring junction, 204Junionone, 9, 10Juniperus, 11, 12Juniperus communis, 9Juniperus sabinus, 12

Kabiramides, 39Kahalalides, 46Kalihinol A, 57–58Kampo, 351Kanamycin, 271, 275Kanamycin A, building blocks and scaffold for,

275Kanchanamycins, 68, 69Kansui, 365, 366Kansuiphorins, 365, 366Karenia brevis, 34, 193KAS domains, 154Kauranes, 17, 18Keeling, Christopher I., x, 127Ketene, 6α-Ketoadipate, 200Ketoadipate N -caprylcysteamine thioester, 199α-Ketoisovalerate, in pantothenate biosynthesis,

249, 251Ketolide, 294Ketopantoate, in pantothenate biosynthesis, 249,

251Ketoreductase (KR) domains, 166, 179–180

classes of, 169in fungal polyketide biosynthesis, 154, 156polyketide double bonds and, 167–169, 171,

172–173, 176Ketoses, 5Ketosynthase (KS), in fungal polyketide

biosynthesis, 145–146Ketosynthase (KS) domain, 149, 150, 152, 153,

154, 155, 165, 166, 172, 178, 179–180β-Ketothiolester, in fungal polyketide

biosynthesis, 145–146Kibdelones, 81, 82Kibdelosporangium, 81Kingston, David G. I., x, 325Kirkpatrichia varialosa, 52Kishi group, 329Kitasatospora kifunensis, 88Kittendorf, Jeffrey D., x, 163Knoevenagel cyclization, 158KR-DH domain pair, 172–173

KS domains, 149. See also Ketosynthase (KS)domain

KSQ domain, for nanchangmycin, 197

L-365, 260, 312Labdanes, 17, 18β-Lactamases, 67–68, 292–293Lactams. See b-lactams (β-lactams)Lactones, 154

enzyme-inhibitory, 85herbicidal, 91

Lactose, 5“Ladder-shaped” polyethers, 32, 34–36, 189,

192, 193chemistry of, 202–204

Laffariella variabilis, 58Lamellaria, 50Lamellarins, 50Lantibiotics, 271Lasalocid, 84, 190, 191–192Laticifers, in terpenoid alkaloid biosynthesis, 221Latrunculia bocagei, 50Latrunculia magnifica, 38Latrunculin A, 38Laurencia, 55, 58Laurencia nipponica, 33Laurencia obtusa, 55Laurencin, 33LDD motif, 169L-dihydroxyphenylalanine (L-DOPA), 25. See

also DOPA decarboxylaseLecanicillium lecanii, 100Lecanicillium longisporum, 100Lee, Kuo-Hsiung, x, 351Legionella pnseumophila, antibiotics against, 70Leinamycin, 170, 175, 176, 181

HMGS-containing biosynthetic pathway for,177

Leishmania, 82Lepadiformine, 54Leupeptins, 86Leurocristine, 327Levopimaradiene, in diterpene resin acid

biosynthesis, 137L-hydroxyl group configurations, polyketide

double bonds and, 169Lignans, 21, 352, 357–358Lignin, 21Liliopsida, 20Limonene, 10–11, 26

in menthol biosynthesis, 133Linalool, 9Lincomycin, 271Lindera strychnifolia, 15

408 INDEX

Linear gramicidin. See GramicidinsLinear peptides, in marine natural products,

44–45Lipoic acid, 242, 243, 258Lipopeptides, as natural products, 76–77Lipstatin, 85, 300, 301Liquid chromatography, in studying terpenoids,

138Liquid chromatography/mass spectrometry

(LC-MS), in antibiotic biosynthesisresearch, 280

Lissoclinum forskalii, 57Lissoclinum patella, 46Listeria, antibiotics against, 70Littorine, 223

in tropane alkaloid biosynthesis, 224Loading component, 150

for NR-PKS, 151–152Loading module, 165Loganin, 10Lomatium suksdorfi, anti-HIV compounds from,

365–367London Pharmacopoeia, 290Long-chain polyunsaturated fatty acids, 25Longifolin, 14, 15Lophocerine, 25Lophogorgia, 56Lophophora schotti, 25Lophophora williamsii, 25Lophotoxin, 56, 57Lovastatin, 93, 143, 147, 148, 149, 155, 309, 310Lovastatin diketide synthase (LDKS), 149,

156–157, 158Lovastatin nonaketide synthase (LNKS), 149,

156–157Lovastatin polyketide synthases, 156–157lovB gene, 156lovC gene, 156lovD gene, 157lovF gene, 156Low-density cholesterol (LDC), 92Low-density lipoproteins (LDLs), 309Low-molecular-weight terpenoids, 127Lupane, 18, 19Lyngbya majuscula, HMGS-containing

biosynthetic pathway of, 177

Macarpine, 211in sanginarine biosynthesis, 214

Macrocyclic bis-3-alkylpiperidine, 47Macrolactone scaffold, 165, 166, 272Macrolides, 68, 143, 147, 293–294

antiparasitical, 82–83gastrointestinal-active, 89

herbicidal, 91–92immunosuppressive, 97–98, 99insecticide, 100–102in marine natural products, 38–41

Macrotetrolide biosynthetic gene cluster, 189Macrotetrolide PKS, nonactin and, 201Macrotetrolides, 190, 200, 201, 202Maculosin, 90Magnaporthe grisea, 148Magneliopsida, 20Maitotoxins, 34, 35, 193, 202, 203, 204Malaria, 134. See also Plasmodium entriesMalonyl-CoA, 26, 151, 152, 154, 178, 181

in antibiotic biosynthesis, 274Malonyl transferase (MT), in fungal polyketide

biosynthesis, 145–146Maltose, 5Mammalian cell cycle, 326Mammalian FAS, 154Mannose, 5Mannose 1-phosphate, in vitamin C biosynthesis,

252Manoalide, 58Manzamines, 47–49, 79, 80Marahiel, Mohamed A., x, 111Marine invertebrates, natural products isolated

from, 31–64Marine natural products, 31–64

antineoplastic agents among, 305–307chemical diversity of, 31–32

Marine natural products chemistry, origins of,31, 32

Marine organisms, polyketides from, 143Marine polyether ladder compounds, 32, 34–36,

189, 192, 193chemistry of, 202–204

Marine polyethers, 189biology and molecular structure of, 189, 190,

192–193Marmesin, 22, 23Mass spectra databases, in studying terpenoids,

138Mass-spectral fragmentation patterns, in studying

terpenoids, 138Matairesinol, 21Materia Medica, 289, 376Matricaria recuitita, 22Maytanprene, 362, 363Maytansine, 362, 363Maytenus chuchuhuasca, 363Maytenus cuzooina, 363Maytenus diversifolia, 362Maytenus emarginata, 362Maytenus illicifolia, 362, 363

INDEX 409

Maytenus ovatus, 362Maytenus serrata, 362Maytenus terpenoids, 362–363Mechanism-of-action (MOA)-based bioassay

methods, 352Mectizan®, 311Medicine

alternative, 351–352antibiotics important in, 271artemisinin in, 134cofactors/coenzymes in, 260–262herbal remedies in, 351–352natural products in, vii, 66plant preparations in, 289–291Taxol® in, 134–135

Melanization, 148Melilotus alba, 22Menaquinone, 240, 255, 256Mentha, 11, 12, 132Mentha arvensis, 12, 15Mentha gentilis, 12Menthane, 10–11Mentha piperita, 12, 15, 130Mentha pulegium, 12Mentha rotundifolia, 12Mentha spirata, 12Menthenol, 12Menthol, 11–12, 127, 130

biosynthesis of, 132–133Menthone, 11, 12

in menthol biosynthesis, 133Merck group, 292, 303Meropenem, 67, 68Meroterpenoid metabolites, 144, 147Meroterpenoids, 8Mescaline, 24, 25Metabolic engineering

of caffeine biosynthesis, 225–226of morphine biosynthesis, 215in studying terpenoids, 139of terpenoid indole alkaloids, 221–222of tropane alkaloids, 224

Metagenomics approach, 103Metal ions

iron/sulfur clusters and, 243in tetrapyrroles, 243

Metals, ionophore complexes with, 190–191Metarhizium anisopliae, 100Methane, in archaeal coenzyme biosynthesis, 257Methanopterin

in archaeal coenzyme biosynthesis, 257biosynthesis of, 245

Methoxyacrylate group, 144Methoxymalonate, in antibiotic biosynthesis, 274

Methoxytabersonine, 219, 2202-Methyl-3-buten-2-ol, 1324-Methylaminobutanal, in tropane alkaloid

biosynthesis, 222Methylation

in antibiotic biosynthesis, 276in nonribosomal peptide synthesis, 112

Methylation (Mt) domain, in nonribosomalpeptide synthesis, 112, 118

Methylation genes, for monensin, 1952-Methylbutane, 72C-Methyl-D-erythritol-4-phosphate (MEP)

pathwayin plant terpenoid biosynthesis, 130, 131in Taxol® biosynthesis, 135

Methyl groups, atypical polyketide domains and,175–176

Methylmalonyl-CoA, in antibiotic biosynthesis,274

3-Methylorcinaldehyde, 150, 1536-Methylsalicylic acid (6-MSA), 143, 147, 148,

149, 150, 154Methyl transferase (Mt) domain, 175, 179–180

in nonribosomal peptide synthesis, 112, 118Methyltransferases, in antibiotic biosynthesis,

276–277Mevacor®, 309Mevalonate, 273

in isoprenoid cofactor biosynthesis, 253, 254as plant biosynthetic building block, 3, 4

Mevalonate (MEV) pathwayplant products from, 7–20in plant terpenoid biosynthesis, 130, 131

Mevalonic acid (MVA), 7 1in antibiotic biosynthesis, 272

Mevastatin, 92–93, 156, 261–262, 310Mevinolin, 93, 156, 309Micafungin, 77, 297, 298Microbial fermentations, drugs derived from,

290–291Microbial host cells, in artemisnin biosynthesis,

134Microbial natural products , 65–108

antibacterials, 66–73, 74–75antifungals, 73–77antiparasitics, 82–84, 85antitumor compounds, 77–82discovery of, 291diversity and applications of, 65–66, 102–103enzyme inhibitors, 84–89future research on, 102–103gastrointestinal motor stimulators, 89herbicides, 90–92hypocholesterolemics, 92–93

410 INDEX

Microbial natural products (Continued)hypoglycemics, 94–95immunosuppressants, 96–100insecticides, 100–102

Micromonospora, 79Micromonospora echinospora, 339Microorganisms

antitumor compounds from, 77–82cofactors from, 239, 230–241marine natural products from, 32natural products from, 65–108pantothenate biosynthesis in, 249–251

Microtubes, 327Microtubules, 332Miglitol, 94Milbemycins, 83Minocycline, 293, 294Mithramycin, 342, 343Mitochondria, coenzyme biosynthesis in, 259Mitomycin family, 303, 304Mitomycins, 339, 341Mitosanes, 339Mitosis, 327. See also Cell cycle“Mix-and-match” approach, in antibiotic

biosynthesis, 279MK-329, 312Models, of plant natural product diversity, 4. See

also Natural product models;Pharmaceutical models

Modificationof antibiotic scaffolds, 276–278in self-protection against antibiotics, 274

Modifying domains, in nonribosomal peptidesynthesis, 112, 117–118

Modular PKSs, in polyketide biosynthesis,165–167

Modular polyketides, 163–187atypical PKS domains in, 175–182diversity and applications of, 163–165double bonds in, 167–175in prototypical polyketide biosynthesis,

165–167Modular polyketide synthases, 163, 165–167Module exchange, in producing novel peptides,

119Modules, in nonribosomal peptide synthesis, 112Molecular biology, in studying terpenoids, 138Mollusks

indole alkaloids from, 51pyrrole alkaloids from, 50

Molybdopterin, 240, 242, 243biosynthesis of, 242, 245, 246effects in humans of genetic defects in

biosynthesis of, 260

Monacolin J, 155Monactin, 190, 201Monascus purpureus, 150monBI gene, 195, 197monBII gene, 195–197monCI gene, 195monCII mutant, 194, 205Monensin, 189Monensin PKS, 194Monensins, 83–84, 190, 191, 192, 204, 271

chemistry of, 194–197Monensinyl N -acetylcysteamine thioester, 195Monobactams, 67, 91, 293Monocerin, 143, 147Monocyclic diterpenoids, 17, 18Monocyclic sesquiterpenoids, 15–17Monolignols, 21Monooxygenases, in antibiotic biosynthesis,

277Monosaccharides, 5

in antibiotic biosynthesis, 273Monoterpene precursors, 9Monoterpenes, 7, 26

biosynthesis of, 131Monoterpenoids, 8–14, 128

biosynthesis of, 133diversity of, 8–9in marine natural products, 55–56menthol as, 132–133

Morphinan, 211, 213, 214, 215Morphine, 24, 25, 210, 212, 299

biosynthesis of, 214–215, 220isolation of, 290in sanginarine biosynthesis, 213–214

Morris-Natschke, Susan L., x, 351MOS biosynthesis, 153Motilides, 89Motilin receptors, 89MSAS gene, 154Multiple sclerosis, 97Mupirocin, 171, 176, 181, 294, 295

HMGS-containing biosynthetic pathway for,177

Mussadine, 48, 49Mutants, preparation of, 205Mutational analysis, in antibiotic biosynthesis

research, 280–281Mycalamides, 42Mycale, 41, 42, 58Mycale hentscheli, 41Mycale izuensis, 46Mycalolides, 39Mycaperoxide A, 58, 59Mycelia sterilia, 97

INDEX 411

Mycobacterium tuberculosis, 164, 165, 259antibiotics against, 70

Mycobacterium ulcerans, 164–165Mycobactin A, 118Mycolactones, 164, 165Mycophenolic acid, 96–97, 144, 147, 308Mycosporine-glycine, 43–44Mycosporines, 43–44Mycotoxins, 144Mylotarg®, 306, 307Myrcene, 8–9Myriocin, 97Myriococcum albomyces, 97Myristica fragrans, 22Myristicin, 22Myrtenal, 12, 13Myrtenol, 12, 13Mytilus galloprovincialis, 33Myurolane, 16Myxococcus xanthus, 181

HMGS-containing biosynthetic pathway of,177

Myxovirescin, 181, 182Myxovirescin A, 171, 176

HMGS-containing biosynthetic pathway for,177

N-acetyl-cysteamine (SNAc), 122NAD, 257

in pyridine nucleotide biosynthesis, 249, 250NADH, 240NADP, in pyridine nucleotide biosynthesis, 249,

250NADPH, 151, 156, 167, 240

in ajmaline biosynthesis, 216in morphine biosynthesis, 214in tropane alkaloid biosynthesis, 224

Nakafuran-9, 55, 56Namicin, 43nanA genes, 197, 198Nanchangmycin, 189, 204

chemistry of, 197–200Nanchangmycin aglycone, 199, 200Naphthalenes, 92–93Naphtho γ-pyrones, enzyme-inhibitory, 87–89Naphthopyrone (YWA1) biosynthesis, 150, 151,

152, 153Naphthoquinone derivatives, 43Napyradiomycin, 276Napyradiomycin A, building blocks and scaffold

for, 275Narasin, 84Narbonolide, 166Narcissus, 301

Naringenin, 22, 23Naringenin chalcone, 26Natamycin, 75–76Natural plant products, maximization of chemical

diversity/and production of, 25–26Natural product models, pharmaceuticals in, 289,

312–313Natural product preparations, history of,

289–291, 291–312Natural Product Reports, 129Natural products

alkaloids, 209–237antibiotics, 269–285as anticancer agents, 325–349benefits of, 342–343cofactors/coenzymes, 239–267defined, 326drug discovery among plant-derived, 351–388as drugs and drug leads, 325–326, 342–343fungal polyketides, 143–161from fungi, 291interest in, viimarine, 31–64, 305–307microbial, 65–108, 291modular polyketides, 163–187nonribosomal peptides, 111–125from plants, 3–29, 289–291plant terpenoids, 127–142polyketide ethers, 189–207preparation of pharmaceuticals from,

289–324from prokaryotes, 291therapeutic applications of, 289

Natural Products Research Laboratory (NPRL),368–369

Navelbine, 353, 354Neisseria gonorrhoeae, antibiotics against, 70Nematodes, antiparasitics against, 82Neoabietadiene, in diterpene resin acid

biosynthesis, 137Neoisomenthol, 11, 12Neomenthol, 11, 12Neopinone, 212

in morphine biosynthesis, 215Neosurugatoxin, 51Neo-tanshinlactone, 360Nepeta cataria, 10Nepetalactone, 10Nerolidol, 14, 15New Drug Application (NDA), 369Newman, David J., x, 325Nicotiana tabacum, 24

412 INDEX

Nicotinamide, 240biosynthesis of, 247–249

Nicotinamide riboside, 240in pyridine nucleotide biosynthesis, 249

Nicotinate, 240Nicotine, 24, 222, 223Nicotinic acetylcholine receptor, 300Nicotinic acid

alkaloids from, 23–24in pyridine nucleotide biosynthesis, 249, 250

Nicotinic acid mononucleotide, in pyridinenucleotide biosynthesis, 250

Nigericin, 190, 192complexes with sodium and potassium, 191

Nigericin I, 189Nitrogen atoms, in alkaloid molecules, 209N-methylation (Mt) domain, in nonribosomal

peptide synthesis, 112, 118N-methylcoclaurine, 213, 215N-methylputrescine, 223

in tropane alkaloid biosynthesis, 222N-methylstylopine, 212N-methylxanthosine, in caffeine biosynthesis,

225NMR structure analysis, of coenzyme

biosynthesis enzymes, 259. See alsoNuclear magnetic resonance (NMR)

Nodulisporic acids, 311–312Nodulisporium, 311Nonactate, 199, 202Nonactate synthase (NonS), 201Nonactic acid, 200, 201Nonactins, 189, 190, 191, 199

chemistry of, 200–202Nonea, 22Non genes, 201Nonreduced (NR) compounds, 149Nonribosomal peptides, 111–125

diversity and biological roles of, 112–114in marine natural products, 43–46synthesis of, 112, 114, 115, 116–118techniques for producing novel, 118–122

Nonribosomal peptide synthetase (NRPS)module, 158, 171

HR PKS and, 158–159Nonribosomal peptide synthetases (NRPSs),

111–112, 113, 156, 172. See alsoPKS/NRPS pathway

in antibiotic biosynthesis, 274catalytic domains of, 114–118future of, 122module and domain exchanges in, 119in producing novel peptides, 118–120, 122single reactions in, 115

Norajmaline, 218Norcoclaurine, 211, 212, 213Norcoclaurine synthases (NCSs), 211, 212–213Norsolorinic acid, 143, 144, 147, 149, 151NorS protein complex, 151Norzoanthamine, 55Noscapine, 211Notoginsenosides, 373Novartis group, 306Novobiocin, 277NRPS/PKS metabolites, in marine natural

products, 42. See also Nonribosomalpeptide synthetases (NRPSs)

NSAS, 151, 152, 153N-terminal docking domain, 166Nuclear magnetic resonance (NMR), 205. See

also NMR structure analysis; REDORNMR studies

in antibiotic biosynthesis research, 280Nucleoside analogs, as insecticides, 102Nucleotides, in antibiotic biosynthesis, 272Nudibranchs, isocyanide-containing natural

products from, 57–58Nystatin, 75, 276

Oceans, species diversity of, 31Ochratoxins, 144, 147Ocimene, 9Ocimium basilicum, 9O’Connor, Sarah E., x, 209Octaketides, 26Oils, 6

of aniseed, 22of blackcurrant, 12of cinnamon, 12of clove, 15of fennel, 22of ginger, 15of hops, 15of mandarin, 14of mint, 132of neroli, 14of orange, 14of star anise, 22

Okadaic acid, 35–36, 190, 192–193Olea europaea, 10Oleanane, 18, 19Oleandomycin, 89Oleuropin, 10Oligomerization, in isoprenoid cofactor

biosynthesis, 256Oligosaccharide antibiotics, 273, 275–276, 278Olistat, 301Omega-6 fatty acids, 25

INDEX 413

Onchocerca volvulus, 311Onchocerciasis, 311Oncovin, 353Onnamide A, 176Onnamides, 42, 171, 182

HMGS-containing biosynthetic pathway for,177

Open-chain polyketides, in marine naturalproducts, 36–38

Opium poppyantipain agents from, 299in morphine biosynthesis, 215in sanginarine biosynthesis, 214

Optional domains, in nonribosomal peptidesynthesis, 112, 117–118

orf genes, 202, 205Ornithine, in tropane alkaloid biosynthesis, 222,

223Oroidin, 48Orsellinic acid, 143, 147, 148, 149, 154

biosynthesis of, 149Orsellinic acid synthase (OSAS), 149Ortataxel, 354, 355Orthodon angustifolium, 12Oryza sativa, terpenoid-synthase-encoding genes

of, 129Ostreopsis siamensis, 37Oxaloacetate, 144Oxidation

in antibiotic biosynthesis, 276in nonribosomal peptide synthesis, 112

Oxidation/oxidase (Ox) domain, 179–180in nonribosomal peptide synthesis, 112, 118

Oxidoreductases, in antibiotic biosynthesis, 277,278

Oxygenase (Oxy) domain, 179–180Oxylipins, 32–33Oxytetracycline, 293, 294OZ-277, 370

P450 monooxygenases, in antibiotic biosynthesis,276, 277

Paclitaxel, 8, 17, 127, 301, 325, 326, 331–332Paederus fuscipes symbiont, HMGS-containing

biosynthetic pathway of, 177Palau’amine, 48, 49Palmitine biosynthesis, 214Palustradiene, in diterpene resin acid

biosynthesis, 137Palythoa, 37Palytoxin, 37Panax, 370Panax ginseng, 370, 371–372Panax japonicus, 371

Panax notoginseng, 371, 373Panax quinquefolium, 371, 372–373Pantetheine, 240Pantoate, in pantothenate biosynthesis, 249, 251Pantothenate, 240

biosynthesis of, 249–251Pantothenic acid, effects in humans of genetic

defects in metabolism of, 260Papaverine, 24, 25Papaver somniferum, 25, 210, 214, 299PAPS (3′-phosphoadenosine-5′-phosphosulfate)

molecule, 174Paraherquonin, 144, 147Parasiticide market, 82Partially reduced (PR) compounds, 149Pateamine, 42Patellamide A, 46Patulin, 143, 147Patupilone, 333P-CTX-1, 190, 193Pectenotoxins, 36Pederins, 42, 171, 176, 182

HMGS-containing biosynthetic pathway for,177

Pelargonidin, 22, 23Pelargonium roseum, 12Pellagra, 249Peloruside A, 40, 41Penares schulzei, 53Penicillanic acid, 67Penicillic acid, 143, 144, 147Penicillin G, 271, 291–292Penicillins, 66–67, 114, 291–292

discovery of, 291Penicillium, 57Penicillium brevicompactum, 96Penicillium chrysogenum, 269, 271Penicillium citrinum, 92, 156, 261Penicillium echinulatum, 96Penicillium madriti, 149Penicillium notatum, 66, 114, 269, 291Penicillium patulum, 150, 154Pentacyclic triterpenoids, 18, 19Pentaketide chromone synthase (PCS), 26Pentoses, 5Pepstatin, 86, 87, 299Peptide antibiotics, 71–73, 74–75Peptide products, from nonribosomal peptide

synthetases, 111–112, 113Peptides

antitumoral, 78–79enzyme-inhibitory, 85–87herbicidal, 90hypoglycemic, 95

414 INDEX

Peptides (Continued)immunosuppressive, 96insecticide, 100, 101nonribosomal, 111–125

Peptidyl carrier protein (PCP) domain, 179–180in nonribosomal peptide synthesis, 112, 114,

115–116, 117, 118in producing novel peptides, 120–122

Peptidyl-thioesters, 122Pernicious anemia, 260–261Peroxidase, in vinblastine biosynthesis, 221Persulfide, 242, 243Pestalotiopsis microspore, 79Petrosia corticata, 33Petrosia seriata, 47Petrosin A, 47, 48Pettit group, 328, 330Phakellia flabellata, 48Pharmaceutical companies, on natural products,

342–343Pharmaceutical industry, modular polyketides

and, 163–165Pharmaceutical models, 312–313Pharmaceuticals, 289–324

Alzheimer’s agents, 301antibacterial agents, 291–296antifungal agents, 296–297, 298antimalarials, 297–298, 299antineoplastic agents, 301–307antiobesity, 300–301antipain agents, 299–300antiparasitic agents, 311–312antivirals, 298–299cardiovascular agents, 308–310immunosuppressant agents, 307–308natural products among, 65–66, 102–103plant terpenoids as, 127

PharmaMar company, 305, 341Phellandrene, 11Phellandrium aquaticum, 11Phenethylisoquinoline alkaloids, 25Phenolic compounds, 6–7Phenolic natural products, diversity of, 20Phenol oxidase, 211Phenylalanine, 20

in Taxol® biosynthesis, 135Phenylalanine hydroxylase deficiency, 260Phenylketonuria, 260Phenyllactic acid, 223, 224Phenyl propanoids, 21, 293Phenylpropenes, 21–22Phloem parenchyma, in terpenoid alkaloid

biosynthesis, 220–221Phoma, 157

Phoma macdonaldii, 92Phorbas, 41Phorboxazole A, 41Phoslactomycins, 171, 173Phosphinothricin, 90Phosphoenolpyruvate (PEP), in antibiotic

biosynthesis, 272Phosphopantetheine, 166

in pantothenate biosynthesis, 250, 251Photosynthesis, 5PhPKS1 gene, 157Phthalascidin, 306Phthalidisoquinoline, 211Phyllidia verrucosa, 57Physostigmine alkaloids, 51Phytanoyl-CoA dioxygenase (PhyH) domain,

179–180Phytohormones, 8Phytol, 17, 18Picea, 130Pictet–Spengler condensation, in terpenoid

indole alkaloid biosynthesis, 216Pikromycin PKS system, 166, 169Pimaricin, 75–76, 276Pimaronyl cation, in diterpene resin acid

biosynthesis, 137Pimeloyl-CoA, in biotin biosynthesis, 253, 254Pimenta acris, 9Pimpinella anisum, 22Pinanes, 12–13Pinenes, 12–13, 26

in menthol biosynthesis, 133Pine trees, diterpene resin acids from, 136, 137Pinna attenuata, 36Pinna pectinata, 36Pinnatoxins, 36Pinocarveol, 12, 13Pinocarvone, 13Pinoresinol, 21Pinus, 11, 130Pinus longifolia, 12Piperine, 23, 24Piperitol, 11, 12Piperitone, 11, 12Piper nigrum, 15, 23Pirirubicin, 336Pitavastatin, 309, 310pksA gene, 158PKS domains, atypical, 175–182. See also

Polyketide synthase (PKS)PKS genes, 153

linking to PKS compounds in fungi, 148–149PKSN, 158

INDEX 415

PKS/NRPS metabolitesin antibiotic biosynthesis research, 281in marine natural products, 42

PKS/NRPS pathway, 182, 204in antibiotic biosynthesis, 274HMGS-containing, 179–180

PKS pathway, 182HMGS-containing, 179–180

PKS proteins, 148, 149PksX pathway, 181, 182Plakina, 54Plakinamine, 54Plakortis, 33Plant alkaloids, 209–237Plant biosynthetic pathways, for alkaloids,

210–215, 216–222, 222–224, 224–226Plant natural products, 3–29

biosynthetic building blocks of, 3chemical diversity of, 4, 5drug discovery among, 351–388origin of, 4

Plant preparations, therapeutic applications of,289–290

Plantsantitumoral steroid alkaloids from, 79, 80carbohydrates from, 4–6coenzyme biosynthesis in, 259coenzymes from, 240–241diversity of, 3isoprenoid cofactor biosynthesis in, 256natural products from, 289–291pantothenate biosynthesis in, 249–251polyketides from, 143pyridine nucleotide biosynthesis in, 249terpenoids in, 7–20, 127–142tetrapyrrole biosynthesis and, 243thiamine pyrophosphate biosynthesis in, 247vitamin C biosynthesis in, 251–252vitamins in, 239

Plasmodium, 82, 259Plasmodium falciparum, 134, 192, 259, 298, 312,

370Plastids, 259

isoprene biosynthesis and, 130–132Platanic acid, 368Platencin, 313Platensimycin (PTM), 95, 313Pleuromutilin, 271Plocamium cartilagineum, 55Pneumocandin B, 76Pneumocandin Bo, 297Pneumocystis carinii, lipopeptides against, 76Podophyllotoxins, 21, 302, 303, 335–336, 337,

357, 358

Podophyllum, 302, 357Podophyllum emodi, 357Podophyllum hexandrum, 357Podophyllum lignans, 352, 357–358Podophyllum peltatum, 335, 357Pogonins, 101, 102Poisoning, by marine polyethers, 192Polyacetylenes, in marine natural products, 33Polyamine alkaloids, in marine natural products,

47, 53Polycitones, 50Polyene antibiotics, 73–76Polyene lactone, amphotericin as, 297Polyene–polyepoxide model, of polyether

formation, 189Polyether antibiotics, 189Polyethers

antiparasitical, 83–84, 85in marine natural products, 34–36

Polyketide antibiotics, biosynthesis of, 272, 274Polyketide biosynthesis

fungal, 144–148, 149, 150–157prototypical, 165–167termination of, 173–175

Polyketide double bonds, 167–175cis double bonds, 169–173, 173–174, 182terminal double bonds, 173–175trans double bonds, 167–169, 171–172, 173,

176, 182Polyketide drugs, clinically relevant, 164Polyketide ethers, 189–207

biology and molecular structure of, 189–193chemical tools and techniques for studying,

204–205chemistry of, 194–204

Polyketide polyethers, as antibiotics, 191Polyketides, 6

antibacterial, 68–71, 72antitumoral, 81, 82aromatic, 6–7diversification of, 175diversity and functions of, 143–144in fungi, 143–161in marine natural products, 32–43modular, 163–187open-chain, 36–38synthesis of, 143

Polyketide synthase (PKS), 26, 143. See alsoPKS entries

in fungal polyketide biosynthesis, 146–148,149

in polyketide biosynthesis, 165–167Polymerase chain reaction (PCR) primers,

148–149

416 INDEX

Polymixins, 73, 75Polyneuridine aldehyde, 218Polypeptides, from monensin gene cluster, 196.

See also PeptidesPolyprenyl diphosphate, 255, 257Polypropionates, in marine natural products,

33–34Polysaccharides, 5–6

in marine natural products, 59Polysitor, 50Polysyncraton lithostrotium, 43Polyterpenes, 7Polyterpenoids, 128Polytheonamide B, 45Polyunsaturated fatty acids, 25Poplar isoprene synthase, 132Populus, 130Populus trichocarpa,

terpenoid-synthase-encoding genes of, 129Porphobilinogen, 244

in tetrapyrrole biosynthesis, 243Porphyria, 260Porphyrin biosynthetic enzyme deficiencies, 260Porphyrins, 240Potassium, 191Pravachol®, 309Pravastatin, 309, 310Precursors

of antibiotics, 271–272, 273biosynthesis of coenzyme, 258for coenzyme biosynthesis, 241in fungal polyketide biosynthesis, 145of plant terpenoids, 128, 130vitamins as, 239

Precursor Z, 246Prefusarin, 155, 158Premonensin, 194, 195Prenyl transferases, 130Primary health care, plant products as, 290Primary metabolites

antibiotics and, 269, 271–273natural products as, 65–66, 351plant terpenoids as, 127, 128

Pristimerin, 362, 363Pristinamycin, 71, 72Processing component, 150Prodiginines, 98–99Prodigiosin, 80, 99

structure of, 98Product template (PT) domain, 149, 150, 152,

154, 156Programming, in fungal polyketide biosynthesis,

148Prokaryotes, natural products from, 291

Prokaryotic biosynthetic pathways, for alkaloids,210

Propionate, 200Prorocentrum lima, 192Prostaglandins, 33Prostanoids, 33Protein kinase C, 303Proteins

compounds targeting/interacting with, 325,326–338

in polyketide synthesis, 143Proteus, β-lactams effective against, 68Protocatechoic acid, 20Protoceratium, 193Protoceratium reticulatum, 35Proton pump, 256Protopanaxadiol, 371Protopanaxatriol, 371Protoperidinium crassipes, 36Protopine, 211, 212

in sanginarine biosynthesis, 214Protozoa, coenzyme biosynthesis in, 259Psammaplin A, 44Psammaplysilla purpurea, 44Psammaplysin A, 44Pseudaxinyssa cantharella, 44Pseudoalteromonas, 52Pseudoalteromonas denitrificans, 99Pseudoaxinyssa pitys, 58Pseudoceratina purpurea, 44Pseudoginsenoside, 373Pseudoguaiane, 16Pseudomonas, β-lactams effective against, 68Pseudomonas aeruginosa, 95, 293Pseudomonas fluorescens, 294

HMGS-containing biosynthetic pathway of,177

Pseudomonas magnesiorubra, 99Pseudomonas syringae, 91Pseudomonic acid, 294Pseudopterogorgia elisabethae, 56Pseudopterosin A, 56, 57Psoralen, 22, 23Ptilocaulis spiculifer, 52Ptilomycalin A, 52Pueraria montana, 130Puffer fish poisoning, 52Pulegol, 11, 12Pulegone, in menthol biosynthesis, 133Punaglandins, 33Punica granatum, 23Purine, in caffeine biosynthesis, 225Purine alkaloids, 209, 210, 224–226Purine analogs, enzyme-inhibitory, 87

INDEX 417

Purine biosynthesis, in thiamine pyrophosphatebiosynthesis, 245

Putrescine, in tropane alkaloid biosynthesis, 222,223

Pyrethric acid, 9, 10Pyridine nucleotides

biosynthesis of, 247–249, 250iron/sulfur clusters and, 242–243

Pyridoacridines, in marine natural products, 47,49–50

Pyridollium ion, in tropane alkaloid biosynthesis,222

Pyridopyrropyrimidine alkaloids, 52Pyridoxal, 257

in thiamine pyrophosphate biosynthesis, 247Pyridoxal 5′-phosphate, 240, 258

biosynthesis of, 247, 249in isoprenoid cofactor biosynthesis, 255in thiamine pyrophosphate biosynthesis, 248

Pyridoxine ring, in vitamin B6, 249Pyrimidine precursor, in thiamine pyrophosphate

biosynthesis, 245, 248Pyrimidine ring, coenzymes with, 245Pyrone, 158Pyrone synthase (PS) domain, 179–180Pyrrole alkaloids, in marine natural products, 50Pyrrole compounds

antitumoral, 79–81immunosuppressive, 98–100

Pyrrole-imidazoles, in marine natural products,47, 48–49

Pyrrolidine ring, 67, 68Pyrrolinium ion, in tropane alkaloid biosynthesis,

222Pyrroloquinoline quinone (PQQ), biosynthesis of,

252–253Pyruvate, 255

Qinghao, 369–370Quinine, 297–298

isolation of, 290Quinolines, 217

in marine natural products, 53Quinolinic acid, in pyridine nucleotide

biosynthesis, 247–249, 250bis-Quinolizadine, 47Quinolizidines, in marine natural products,

53–54Quinupristin, 294, 296

Ramoplanin, 71, 74, 294, 295, 296Rapamycin, 97–98, 164, 308Ras protein family, 262Rational bioengineering, 167, 357

Raubasine, 219Rauwolfia, 218Rauwolfia serpentina, 216, 219R domains, for NR-PKS, 153Rebeccamycin, 334–335, 337Recognition, in nonribosomal peptide synthesis,

112Red algae

diterpenoids from, 56monoterpenoids and sesquiterpenoids from, 55sesterteopenoids, triterpenoids, and steroids

from, 58–59REDOR NMR studies, of paclitaxel, 332. See

also Nuclear magnetic resonance (NMR)Reductases (R), 129, 152, 153Reduction (R) domain

in nonribosomal peptide synthesis, 112NRPS module, 158

Regiochemistry, 163, 167in fungal polyketide biosynthesis, 145

Regulation, of antibiotic biosynthesis, 273–274Regulatory genes

in antibiotic biosynthesis, 278–279for monensin, 195

Reminyl®, 301Reniera, 53Renieramycin A, 53, 54Reniera sarai, 47Resin ducts, plant terpenoids from, 128Resistance, to antimalarials, 298Resveratrol, 22, 23Retention indices, in studying terpenoids, 138Reticulines, 25, 211, 212, 213

in berberine biosynthesis, 213in morphine biosynthesis, 214, 215

Retinal, 240, 256Retinol, 255, 256Retrobiosynthetic analysis, of polyether ladder

compounds, 202Rhamnose, 5Rhamnus, 7Rheumatoid arthritis, 96Rhizopus, 165Rhizoxin, 164, 165Rhodobacter, 243Rhombic Fe/S cluster, 242Ribes nigrum, 12Riboflavin, 240, 246, 258

in archaeal coenzyme biosynthesis, 257Ribose, 5Ribosomal peptides, 43

nionribosomal peptides vs., 111–112Ribosomes, antibiotics biosynthesized in, 271

418 INDEX

Ribulose-5-phosphate, in pyridoxal phosphatebiosynthesis, 247, 249

Rice seedling blight, 165Rifabutin, 70Rifampicin, 70Rifamycins, 70, 71, 271Rifapentine, 70, 71Rifaximin, 70, 71Ring cleavage, polyketides and, 143–144Ritterazines, 54–55Ritterella tokioka, 54RNA (ribonucleic acid), compounds

targeting/interacting with, 325, 326,338–341

Rodrıguez-Sanoja, Romina, x, 65Rohdich, Felix, x, 239Rosmarinus officinalis, 13Rosuvastatin, 309, 310Rubitecan, 356, 357Rubrofusarin B, 87, 88Ruiz, Beatriz, x, 65Rumensin®, 192Rutin, 22, 23

Sabinene, 12, 13Saccharomyces cerevisiae, 87, 134, 154Saccharopolyspora, 99Saccharopolyspora erythraea, 68, 89, 164, 271Saccharopolyspora pogona, 101Saccharopolyspora spinosa, 100, 271, 311S-adenosylmethionine (SAM)

in antibiotic biosynthesis, 276–277in fungal polyketide biosynthesis, 146

Salicylic acid, 20isolation of, 290

Salicylihalamide A, 41Salinispora, 338Salinispora tropica, 304Salinomycin, 84, 85Salinosporamide A, 304, 338Salmonella, β-lactams effective against, 68Salutaridine, 212

in morphine biosynthesis, 214Salutaridinol, 212

in morphine biosynthesis, 214, 215Salutaridinol-7-O-acetate, 212Salvia miltiorrhiza, 359, 360Salvia officinalis, 13, 359Salvia terpenoids, 359–362Sanchez, Sergio, x, 65Sanchi ginseng, 370, 371, 373Sandaracopimaradiene, in diterpene resin acid

biosynthesis, 137Sanginarine, 211, 212

biosynthesis of, 213–214Saponins, 18–20, 373Sarain A, 47, 48Sarcodictyn A, 57Sarcodictyon roseum, 57Saturated fatty acids, 6Saxitoxin, 52Scaffolds. See also Building blocks;

Macrolactone scaffoldin antibiotic biosynthesis, 269, 272, 273,

274–276, 276–278, 278–279antibiotic biosynthesis genetics and, 278–279of antibiotics, 296assembly of antibiotic, 274–276modification of antibiotic, 276–278

Scalaradial, 58Scalaranes, 58Sceptrin, 48, 49Schoenafinger, Georg, x, 111Schulzeine A, 53Scopolamine, 222, 223, 224

biosynthesis of, 224in tropane alkaloid biosynthesis, 224

Scopolia, 222Scopulariopsis candida, 91Scoulerine, 212

in berberine biosynthesis, 213Screening Hypothesis, 4Screening libraries, 103Screening techniques, 291Scytonema hofmanni, 91Sea hare, 305seco-cardinane, 16seco-iridoids, 10Secologanin, 10, 217, 220–221

in terpenoid indole alkaloid metabolicengineering, 221

Secondary metabolitesalkaloids as, 209antibiotics as, 269, 271–273natural products as, 65–66, 103, 351peptides as, 111, 114from plants, 3–4, 5plant terpenoids as, 127, 128polyketides as, 143, 163

Securiflustra securifrons, 51Securine A, 51SEK4, 26SEK4b, 26Selectivity-conferring code, of nonribosomal

peptide synthetases, 119Self-protection mechanism, against antibiotics,

273, 274, 278–279Selinene, 26

INDEX 419

Senecionine, 23, 24Separation, in studying terpenoids, 136–138Serratia marcescens, 80, 99Serratia plymuthica, 99Sesamin, 21Sesquiphellandrene, 15, 17Sesquisabinene, 15, 17Sesquiterpenes, 7, 26

biosynthesis of, 131Sesquiterpenoids, 14–17, 128

artemisinin as, 134diversity of, 14–15in marine natural products, 55–56

Sesterterpenes, 7Sesterterpenoids, in marine natural products,

58–59Sherman, David H., x, 163Shikimate, as plant biosynthetic building block,

3, 4Shikimate pathway

in archaeal coenzyme biosynthesis, 257GTP-related coenzymes biosynthesized via,

245plant products from, 20–22

Shikimic acid, 20Shishijimicins, 43Siberian ginseng, 370, 371, 373–374Siletecan, 356, 357Simpson, Thomas J., x, 143Simvastatin, 93, 309, 310Sinapic acid, 20Sinapyl alcohol, 21Singh, Sheo B., x, 289Sinococculine, 362Sinulamide, 53Siphochalina siphonella, 59Sipholenone B, 58–59Siphonaria grisea, 34Siphonaria zelandica, 34Siphonarienal, 34Siphonarin, 34Sirolimus®, 308Sociohormones, 8Sodium, 191Sodium artesunate, 370Sodium channels, polyethers and, 193Soft corals, diterpenoids from, 56–57Solanapyrone A, 157–158Solid-phase microextraction (SPME), in studying

terpenoids, 136–138Solid-phase peptide synthesis (SPPS), for

producing novel peptides, 120, 121SOMT (scoulerine 9-O-methyltransferase), 211Sorafenib, 342–343

Sorangium cellulosum, 81, 164, 172, 332Soybean, 25Sparteine, 24Spatoglossum schmittii, 56Spatol, 56Specialized cells, plant terpenoids from, 128Specificity code for A domain, changing,

119–120Spermine, in pantothenate biosynthesis, 249, 251Spinosad, 100–101, 102Spinosyns (spinosins), 100–101, 102, 271, 311Spiramycin, 68, 69Spirastrella coccinea, 40Spirastrellolide, 40Sponges

3-alkylpiperidines from, 47–48aromatic polyketides from, 43diterpenoids from, 56, 57guanidine alkaloids from, 52indole alkaloids from, 51isocyanide-containing natural products from,

57–58macrolides from, 38–41monoterpenoids and sesquiterpenoids from,

55–56nonribosomal peptides from, 43–46PKS/NRPS metabolites from, 42polyamine alkaloids from, 53pyridoacridines from, 49–50pyrrole alkaloids from, 50pyrrole-imidazoles from, 48–49quinolines and isoquinolines from, 53sesterteopenoids, triterpenoids, and steroids

from, 58–59steroidal alkaloids from, 54terpenoids from, 55

Spongia officinalis, 56Spongionella gracilis, 56Spongiothymidine, 298–299Spongistatins, 39–40Spongosorites ruetzleri, 51Spongouridine, 31, 32, 298–299Sporotricholone, 88Sporotrichum, 88SQ20475, 309, 310Squalene, 18Squalene-derived polyethers, 58Squalene synthase, 144Squalestatins, 144, 147Squalestatin S1, 155, 157Squalestatin S1 polyketide synthases, 157Squalestatin tetraketide intermediate, in fungal

polyketide biosynthesis, 146

420 INDEX

Squalestatin tetraketide synthase (SQTKS), 157,158

Staphylococcus aureus, β-lactams effectiveagainst, 68

Starter unit, 149for antibiotic biosynthesis, 279–280in conventional modular type I PKS, 166for NR-PKS, 151–152polyketide diversification and, 175

Starter unit loading domain (SAT), 149for NR-PKS, 151–152, 153, 154, 156

Statine, 299Statins, 92–93, 309, 310Staurosporine, 303, 304, 336–337, 338Stelletta, 49, 53, 54Stellettadine A, 53Stellettamine A, 54Stellettazole A, 53Stereochemistry

in fungal polyketide biosynthesis, 145of polyketide ethers, 194–204in studying terpenoids, 138

Sterigmatocystin, 152Steroidal alkaloids, 23

antitumoral, 79, 80in marine natural products, 54–55

Steroids, 17–20in marine natural products, 58–59

Stigmastane, 18, 19Stilbenes, 22, 23Storniamides, 50Streptogramins, 70–71, 72, 294Streptomyces, 81, 291, 293, 303

antibiotic biosynthesis regulation in, 273–274Streptomyces achromogenes, 342Streptomyces ambofaciens, 68Streptomyces antibioticus, 78Streptomyces atroolivaceus, HMGS-containing

biosynthetic pathway of, 177Streptomyces aureofaciens, 271Streptomyces avermitilis, 82, 271, 311Streptomyces cattleya, 67Streptomyces cinnamonensis, 83, 194, 196, 197,

205, 271Streptomyces clavuligerus, 67Streptomyces coelicoflavus, 94Streptomyces coelicolor, 99, 196Streptomyces filipinensis, 76Streptomyces griseochromogenes, 98Streptomyces griseoviridis, 80Streptomyces griseus, 200, 202, 293Streptomyces hygroscopicus, 83, 90, 91, 97, 164,

308Streptomyces kanamyceticus, 271

Streptomyces lavendulae, 261Streptomyces lincolnensis, 271Streptomyces lividans, 201Streptomyces longisporus, 99Streptomyces nanchangensis, 197, 205Streptomyces natalensis, 76Streptomyces nodosus, 73, 271Streptomyces noursei, 75Streptomyces orientalis, 294Streptomyces peucetius, 81Streptomyces pimprina, 76Streptomyces platensis, 95Streptomyces plicatus, 342Streptomyces roseosporus, 271, 294Streptomyces teicomyceticus, 294Streptomyces tendae, 95Streptomyces toxytricini, 85, 300Streptomyces tsukubaensis, 97, 307–308Streptomyces verticillus, 78Streptomyces virginiae, HMGS-containing

biosynthetic pathway of, 177Streptomyces viridochromogenes, 90, 271Streptomyces yokosukaensis, 86Streptomyces zelensis, 79Streptomycin, 293, 294Streptoverticillium rubrireticuli, 99Streptozotocin, 342, 343Strictosidine, 217

in ajmaline biosynthesis, 216in terpenoid indole alkaloid biosynthesis, 216in vindoline biosynthesis, 220

Strictosidine glucosidase, in terpenoid indolealkaloid metabolic engineering, 221–222

Strictosidine synthase, in terpenoid indolealkaloid metabolic engineering, 221–222

Strobilurins, 144, 147Structural determination, in studying terpenoids,

138Structural diversity, of terpenoids, 139Strychnine, isolation of, 290Strychnos, 217Strychnos nux vomica, 10Styelsamine D, 49Stylissa carabica, 48Stylissadine A, 48Stylissa mussa, 48Stylopine, 212

in sanginarine biosynthesis, 214Stylotella aurantium, 48Succinate, 200Succinyl-CoA, 244

in vitamin B12 biosynthesis, 241Sucrose, 5

INDEX 421

Sugarsin antibiotic biosynthesis, 272in marine natural products, 59

Suksdorfin, 365, 367Sulfated compounds, in marine natural products,

32Sulfated terpenoids, 55Sulfazecins, 293Sulfolipid-1 (SL-1), 164, 165Sulfolipids, 33Sulfotransferase (ST) domains, 174Surfactin, 113, 116, 117, 119

modifying, 119–120Surfactin synthetase, 119–120Swainsonia canescens, 24Swainsonine, 24Swinholide A, 38–39Synercid®, 294Synthadotin, 330, 331Synthases. See Bacterial modular polyketide

synthases; Biotin synthase; Chalconesynthase (CHS); 6-Deoxyerythronolide Bsynthase; Diterpene synthases; Farnesyldiphosphate synthase (FPPS); Fatty acidsynthase (FAS); Fungal polyketidesynthases; HMG-CoA synthase (HMGS)cassettes; Isoprene synthases; Ketosynthase(KS); Lovastatin polyketide synthases;Modular polyketide synthases; Nonactatesynthase (NonS); Norcoclaurine synthases(NCSs); Orsellinic acid synthase (OSAS);Pentaketide chromone synthase (PCS);Polyketide synthase (PKS); Squalenesynthase; Squalestatin S1 polyketidesynthases; Strictosidine synthase; Terpenoidsynthases (TPSs); Vinorine synthase

Synthesis, in studying terpenoids, 139. See alsoBiosynthesis; Biosynthetic entries

Synthetases. See Bac series synthetases;Gramicidin synthetase; Nonribosomalpeptide synthetase entries; Surfactinsynthetase; Tyrocidine synthetase

Syringium claviflorum, anti-HIV compoundsfrom, 367–369

Syringomycin, 116Syzigium claviflorum, 368

Tabersonine, 219in vindoline biosynthesis, 220

Tabtoxin, 91Tacrolimus®, 97–98, 308Tanshen, 359–360Tanshinone diterpenoids, 360Taprotide, 309, 310

Target modification, in self-protection againstantibiotics, 274

Tasidotin, 330, 331Tautomycetin, 98, 168, 171, 174–175Taxane anticancer drugs, 331, 333Taxane diterpenoids, 26, 301Taxanes, 354Taxol®, 8, 17, 79, 80, 127, 130, 134–136, 139,

301, 302, 303, 305, 325, 331–332, 352,354, 355

biosynthesis of, 135–136Taxomycetes andreanae, 79Taxotere, 354, 355Taxus, 26, 79, 130, 135, 139Taxus baccata, 354Taxus brevifolia, 26, 134, 301, 331, 354Taxus cuspidata, 135Taxus diterpenes, 352, 354–355Taxus wallichiana, 79Tea plants, 225Teicoplanin, 71, 73, 294, 295Telesto ruesei, 33Telithromycin, 294, 295Tendamistat, 95Tenellin, 155, 158Teniposide, 302, 303, 336, 337, 357, 358Tentoxin, 90Terminal double bonds

formation of, 168in polyketides, 173–175

Terpene antibiotics, 273biosynthesis of, 276

Terpene indole alkaloids, 26Terpenes, herbicidal, 92Terpenoid alkaloids, 23Terpenoid indole alkaloids, 209, 210, 216–222

ajmalicine and tetrahydroalstoninebiosynthesis, 219–220

ajmaline biosynthesis, 216–219biosynthesis of, 216diversity and applications of, 216metabolic engineering of, 221–222molecular structures and applications of

representative, 217–219in vinblastine biosynthesis, 221vindoline biosynthesis, 217–219, 220–221

Terpenoidsapplications of, 128approaches to studying, 129biosynthesis of, 130building blocks of, 128chemistry of, 129–136, 137diversity of, 7–8, 127, 128, 129–130with immunosuppressive activity, 96–97

422 INDEX

Terpenoids (Continued)in marine natural products, 55–59in plant interactions, 128in plants, 7–20, 127–142synthesis of, 129tools and techniques for studying, 136–139

Terpenoid synthases (TPSs), 26, 129in biochemical and metabolic terpenoid

engineering, 139isoprene biosynthesis and, 130–132

Terpentecin, 276Terpinene, 11Terpineol, 11, 12Terpinolene, 11Terrestrial bacteria, difficulties in culturing, 103Terrestrial polyethers, biology and molecular

structure of, 189, 190–192Tetracenomycin, 276Tetracyclic triterpenoids, 18, 19Tetracyclines, 271, 293, 294

biosynthesis of, 274Tetrahydroalstonine, 218, 219–220Tetrahydrobiopterin, 240

biosynthesis of, 241, 245, 246, 257effects in humans of genetic defects in

biosynthesis of, 260Tetrahydrocolumbamine, 212Tetrahydrofolate, 240, 257, 261

biosynthesis of, 241, 245, 246in archaeal coenzyme biosynthesis, 257

Tetrahydrofolate derivatives, 258Tetrahydroisoquinoline alkaloids, 53Tetrahydrolipstatin, 300Tetrahydromethanopterin, 246, 2581,3,6,8-Tetrahydroxynaphthalene (THNS), 148,

149, 151–152, 153Tetranactin, 190, 201Tetrapyrroles, biosynthesis of, 243–245Tetraterpenes, 7

biosynthesis of, 131Tetraterpenoids, 128Tetrodotoxin, 52Tetronasin, 190, 192Tetronic acid, 144Thalictrum flavum, 212, 213Thalictrum tuberosum, 213Thebaine, 212

in morphine biosynthesis, 215Theobromine, in caffeine biosynthesis, 225Theonella swinhoei, 38, 42, 45Theonella swinhoei symbiont, HMGS-containing

biosynthetic pathway of, 177Theopederins, 42Therapeutic agents

among natural products, 66, 289nonribosomal peptide synthetases in, 118

Thermotolerance, isoprene in, 132Thermozymocidine, 97Thiamine, 240, 242, 243, 258Thiamine phosphate, in thiamine pyrophosphate

biosynthesis, 248Thiamine precursor, in thiamine pyrophosphate

biosynthesis, 247, 248Thiamine pyrophosphate, 240, 255, 257

biosynthesis of, 245–247, 248, 257Thiazole ring, 81THIC protein, in thiamine pyrophosphate

biosynthesis, 247Thienamycin, 292, 293, 296Thiocolchicines, 359, 360Thiocolchicone, 359, 360Thioesterase (TE) domain, 167, 179–180

in bacterial modular PKS systems, 156in nonribosomal peptide synthesis, 112, 117in producing novel peptides, 120, 121–122terminal polyketide bonds and, 173–175

Thioesterases, 194Thiolation (T) domain, NRPS module, 158Thiolesterase (TE), in fungal polyketide

biosynthesis, 146, 152–153Thiolesters, in fungal polyketide biosynthesis,

146Thiooctanoate, 242, 247Thiophenol, 122Thujanes, 12, 13Thujanone, 12, 13Thuja occidentalis, 12, 13Thujene, 12, 13Thujol, 12, 13Thymol, 11, 12Thymus vulgaris, 12Thyrsiferyl 23-acetate, 58, 59Ticarcilllin, 68Tigecycline, 293, 294Tirucallane, 18, 19tmcJ gene, 175tmcM gene, 175Tobacco leaves, 219Tolypocladium nivenum, 96Topoisomerases, 352

as anticancer agent targets, 326–327compounds that inhibit, 334–335, 335–336

Topotecan, 301, 302, 334, 356Topsentin, 51Traditional Chinese medicine (TCM), 351–352,

376Transcription factors, in terpenoid indole alkaloid

metabolic engineering, 222

INDEX 423

trans double bonds, in polyketides, 167–169,171–172, 173, 176, 182

Translocation, in nonribosomal peptide synthesis,112

trans-polyenes, 202–203Trapoxin B, 312–313Trichoderma polysporium, 307Trididemnum solidum, 46Triketide lactone (TAL), 154Trimethoprim, 261Trinactin, 190, 201Tris-oxazole-containng macrolides, 39Triterpene betulinic acid derivatives, 367–369Triterpenes, 7

biosynthesis of, 131from Ganoderma, 374–376

Triterpenoids, 17–20, 128in marine natural products, 58–59

Tropane alkaloids, 209, 210, 222–224metabolic engineering of, 224molecular structures and applications of

representative, 223Tropine, 223

in tropane alkaloid biosynthesis, 224Tropinone, 223

in tropane alkaloid biosynthesis, 224Tropinone reductases, in tropane alkaloid

biosynthesis, 224Trypanosoma, 82Tryptamine, 217

in terpenoid indole alkaloid biosynthesis, 216Tryptophan

in pyridine nucleotide biosynthesis, 247–249,250

in terpenoid indole alkaloid biosynthesis, 216in terpenoid indole alkaloid metabolic

engineering, 221Tryptophan decarboxylase, in terpenoid indole

alkaloid biosynthesis, 216T-toxin, 143, 147, 148, 155Tubocurarine, 24, 25, 290Tubulin, 352Tubulin assembly

compounds that inhibit, 327–331compounds that promote, 331–333

Tubulins, 40, 41, 301, 303, 306as anticancer agent targets, 326–327

Tung Chung Hsia Tsao, 376Tunicates

diterpenoids from, 57enediynes from, 43heptaprenoids from, 59indole alkaloids from, 51–52macrolides from, 38, 41

nonribosomal peptides from, 43, 44–45, 46pyridoacridines from, 49–50pyrrole alkaloids from, 50quinolines and isoquinolines from, 53quinolizidines and indolizidines from, 53–54steroidal alkaloids from, 54–55

Turbomycins, 103Turmeric, 363–365Type I modular PKSs, in polyketide biosynthesis,

165–167Type II thioesterases, 194Tyrocidine, 112, 113, 116, 117Tyrocidine synthetase, 120Tyrosine, 20, 211

in pyrroloquinoline quinone biosynthesis,252–253

Tyrosine decarboxylase, 211

Ubiquinone, 240, 253, 255, 256UCN-01, 336–337, 338Umbelliferone, 22, 23Undecylprodigiosin, 99United States, medicinal plant products in, 290.

See also Food and Drug Administration(FDA), U.S.

United States National Cancer Institute (NCI),301, 305, 329, 357, 358

Unsaturated carbon–carbon bonds, 167. See alsoPolyketide double bonds

Unsaturated fatty acids, 6Uracil, in pantothenate biosynthesis, 249–250,

251Urochordamine A, 51Uroporphyrinogens, 244

in vitamin B12 biosynthesis, 241Ursane, 18, 19U.S. Food and Drug Administration (FDA), 301,

328, 341

Valepotriates, 10Valeremane, 16Valerian, 10Valeriana officinalis, 10Validamine, 94Valienamine, 94Valrubicin, 336Valtrate, 10Vancomycin, 71, 72, 112, 113, 116, 271, 272,

276, 294, 295, 296building blocks and scaffold for, 275resistance to, 296

Vapor-phase collection, in studying terpenoids,136

Variabilin, 58

424 INDEX

Variolin B, 52Vegetable caterpillars, 376Velban, 353Vellosamine, 218

in ajmaline biosynthesis, 216–218Verbenol, 12, 13Verbenone, 12, 13Verticillium balanoides, 88Veterinary medicine, natural products in, 66Vibralactone, 85Vibrio, 52Vibrio gazogenes, 99Vibrio psychroerythrus, 80, 99Vinblastine, 8, 217, 221, 301–302, 325, 326,

327–328, 353Vinca alkaloids, 301–302

history of, 327–328Vincaleukoblastine, 327Vinca rosea, 327, 353Vincristine, 8, 217, 301–302, 325, 327–328, 353Vindesine, 302, 327–328, 353, 354Vindoline, 219, 220–221

in vinblastine biosynthesis, 221Vinflunine, 327, 353, 354Vinorelbine, 302, 327–328, 353, 354Vinorine, 218

in ajmaline biosynthesis, 216–218Vinorine hydroxylase, 218Vinorine synthase, 218Virginiamycin, 71Virginiamycin M, 171, 176

HMGS-containing biosynthetic pathway for,177

Viridicatumtoxin, 144, 147Viruelnce factors, 164Vitamin A, 253, 262Vitamin B1, 240

biosynthesis of, 241, 247Vitamin B2, 240, 262

biosynthesis of, 241, 245Vitamin B5, 249Vitamin B6, 242

biosynthesis of, 247, 249in thiamine pyrophosphate biosynthesis, 247

Vitamin B12, 240, 262biosynthesis of, 241, 257effects in humans of genetic defects in

metabolism of, 260–261tetrapyrrole biosynthesis and, 243–245

Vitamin C, 5, 240, 262biosynthesis of, 241, 251–252

Vitamin D, 253biosynthesis of, 256

environmental factors modulating biosynthesisof, 262

Vitamin D1, 256Vitamin E, 253, 256, 262Vitamin H, 253Vitamin K, 240, 253Vitamin production, harnessing biosynthetic

pathways for, 262Vitamins, in plants and animals, 239Vitis vinifera, terpenoid-synthase-encoding genes

of, 129Volatile organic compounds (VOCs), isoprene

among, 130–132Vomilene, 218Vomilenine, 218

Wagner-Meerwein 1,2-methyl shift, in diterpeneresin acid biosynthesis, 137

Wakayin, 49, 50Wangiella dermatitidis, 152Warhead chemotherapeutic agents, 341WAS chain extension component, 153WAS CLC domain, 150, 151, 152–153Willow tree preparations, 290World Health Organization (WHO), 290World War II, penicillin during, 291Wyeth group, 306

Xanthine oxidase (XO), 87Xanthosine, in caffeine biosynthesis, 225Xenia elongata, 56Xenical, 300Xenicanes, 56Xenicin, 56, 57Xenovulenes, 144, 147Xestospongia, 47Xestospongia exigua, 43Xestospongin C, 47, 48X-ray crystallography, of coenzyme biosynthesis

enzymes, 259Xylose, 5

Yeasts, 103, 262in biochemical and metabolic terpenoid

engineering, 139thiamine pyrophosphate biosynthesis in, 247,

248vitamin C biosynthesis in, 251–252

Yessotoxins, 35, 36, 190, 193, 202Yuexiandajisus, 365, 366YWA1. See Naphthapyrone (YWA1) biosynthesis

Zearalenone, 143, 144, 147, 151, 152Ziconotide, 300

INDEX 425

Zinc finger proteins, in terpenoid indole alkaloidmetabolic engineering, 222

Zingiberine, 15, 17Zingiber officinalis, 15Zingiber zerumbeticum, 15–17Zinniol, 92ZK-EPO, 333

Zoanthamines, 55Zoanthus, 55Zocot®, 309Zooshikella rubidus, 99Zotchev, Sergey B., x, 269Zwitterionic metal–ionophore complexes,

190–191