Comprehensive Natural Products II: Chemistry and Biology: Natural Products Structural Diversity-I Secondary Metabolites Organization and Biosynthesis Volume 1

Annotation. This work presents a definitive interpretation of the current status of and future trends in natural products-a dynamic field at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids, and enzymes. With more than 1,800 color figures, Comprehensive Natural Products II features 100% new material and complements rather than replaces the original work (©1999). * Reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine * Stimulates new ideas among the established natural products research community-which includes chemists, biochemists, biologists, botanists, and pharmacologists * Informs and inspires students and newcomers to the field with accessible content in a range of delivery formats 1 CONAP_Contents_all_volumes......Page 1 Overview and Introduction......Page 13 Introduction......Page 16 Oleic Acid......Page 18 Soluble (plant) stearoyl ACP Delta9 desaturase......Page 19 Membrane-bound (microbial and animal) Delta9 desaturases......Page 25 Regiochemical Variants of Delta9 Desaturation......Page 27 (Z)-4-Hexadecenoic acid......Page 28 (Z)-6-Hexadecenoic acid......Page 29 (Z/E)-11-Tetradecenoic acid......Page 30 Methylene-Interrupted Polyunsaturated Fatty Acids......Page 31 alpha-Linolenic Acid......Page 33 Ricinoleic Acid......Page 35 Crepenynoic Acid......Page 36 Conjugated Fatty Acids......Page 37 Sterculic Acid......Page 38 Abbreviations......Page 39 References......Page 40 Prostaglandin Endoperoxide Synthases: Structure, Function, and Synthesis of Novel Lipid Signaling Molecules......Page 45 Introduction......Page 46 Regulation of PGHS by Reactive Nitrogen Species......Page 47 S-Nitrosation......Page 48 Lessons from Targeted Deletion and Exchange of PGHS-1 and PGHS-2......Page 50 Partnering between Monomers in PGHS Homodimers......Page 51 Molecular and Kinetic Mechanisms of Prostaglandin Biosynthesis......Page 53 Molecular Determinants of Substrate Binding and Prostaglandin Biosynthesis......Page 55 Control of carbon ring cyclization in prostaglandin biosynthesis......Page 56 Oxygenation of Arachidonic Acid by Acetylated PGHS-2......Page 57 Bis-dioxygenation of eicosapentaenoic acid......Page 59 3-Hydroxyeicosatetraenoic acid......Page 60 20-Hydroxyeicosatetraenoic acid......Page 62 Metabolism of PGH2-Glycerylester and Its Products......Page 63 Pharmacologic Actions of Prostaglandin-Glycerylesters......Page 64 Synthesis of Prostaglandin-Ethanolamides in Cells and In Vivo......Page 65 Abbreviations......Page 66 References......Page 67 Mycolic Acid/Cyclopropane Fatty Acid/Fatty Acid Biosynthesis and Health Relations......Page 74 Introduction......Page 75 Structural Varieties of Mycolic Acids......Page 76 Biosynthesis of the Fatty Acid Core......Page 79 Modifications to the Meromycolate Core Structure......Page 81 Structural Effects of Mycolic Acids on the Cell Envelope......Page 87 Thiacetazone and its impact on cyclopropane synthesis......Page 89 Variability of mycolic acid structures in the BCG vaccine......Page 90 Structural Features of TDM......Page 91 Synthesis......Page 93 The role of antigen 85 in TDM biosynthesis......Page 94 Crystal structure......Page 95 Enzymology......Page 96 Inhibitor development......Page 97 The Immunopathology of TDM......Page 98 The structure-activity relationship of granuloma formation......Page 99 The lsquocytokine storm’ response to TDM......Page 100 Biological properties of antigen 85......Page 101 Vaccine potential of TDM and antigen 85......Page 102 CD1 - A Mammalian Lipid Recognition System......Page 103 CD1 subtypes and lipid partners......Page 104 Sulfolipids......Page 106 Sulfolipid biosynthesis......Page 108 Phthiocerol Dimycocerosates......Page 110 The Phenolic Glycolipids......Page 114 PDIM-less mutant strains of Mtb as vaccine candidates......Page 115 Biosynthesis of LAM......Page 117 Immunopathogenesis......Page 120 Glycopeptidolipids and Sliding Biofilms......Page 121 Biosynthesis of GPLs......Page 123 Structure......Page 125 Biosynthesis......Page 127 Current models for mycobacterial iron trafficking......Page 129 Mycobactins and their analogues as antimicrobials......Page 132 Immunology of mycobactin......Page 133 Mycolactones......Page 135 Structure......Page 136 Function......Page 138 Biosynthesis......Page 139 Abbreviations......Page 140 References......Page 142 Introduction......Page 155 Plant Type III PKSs......Page 157 RppA (1,3,6,8-Tetrahydroxynaphthalene Synthase)......Page 159 Gcs......Page 162 SrsA......Page 164 DpgA......Page 165 Type III PKSs from Mycobacterium......Page 166 PhlD......Page 167 Type III PKSs from Myxobacteria......Page 169 Type III PKSs from Dictyostelium discoideum (Steely 1, 2 (StlA, B))......Page 171 Conclusions and Future Perspectives......Page 173 Abbreviations......Page 175 References......Page 176 Introduction......Page 179 Functional Diversity and Catalytic Potential......Page 182 Chalcone Synthase......Page 186 Benzophenone Synthase......Page 189 Stilbene Synthase......Page 195 Coumaroyl Triacetic Acid Lactone Synthase and Stilbenecarboxylate Synthase......Page 199 Cannabis sativa Polyketide Synthase-1......Page 200 2-Pyrone Synthase......Page 203 Aloesone Synthase......Page 207 Hexaketide Synthase and Octaketide Synthase......Page 209 Enzyme Structure and Site-Directed Mutagenesis......Page 213 Protein Engineering......Page 222 Combinational Biosynthesis......Page 223 Abbreviations......Page 228 References......Page 229 Type II PKS......Page 234 PKS priming......Page 235 Chain assembly and control of chain length......Page 239 Cyclizations and ring topologies......Page 242 Oxidoreductases......Page 243 Halogenases......Page 245 Natural Products Derived from Decaketides that Undergo Initial 7,12-Cyclization......Page 246 Chartreusins......Page 249 Tetracycline folding......Page 252 Angucycline folding......Page 255 Typical angucyclinones/angucyclines (urdamycins, landomycins, and oviedomycin)......Page 256 Angucyclinone-derived natural products with significantly deviated scaffolds (gilvocarcins, jadomycins, kinamycins)......Page 264 Discoid folding......Page 269 Natural Products Derived from Larger Polyketides......Page 273 Angucylines from angular heterocyclic folding......Page 276 Artificial Structural Diversity through Combinatorial Biosynthesis......Page 277 New aromatic polyketides by manipulation of the PKS and PKS-associated enzymes......Page 279 Artificial aromatic polyketides through utilization of enzymes involved in the priming process......Page 280 Nitrogen-containing unnatural polyaromatic compounds using amidotransferase OxyD of the oxytetracyclin pathway......Page 282 New dodecaketides by manipulation of various PKS-associated enzymes involved in benastatin biosynthesis......Page 285 Exploiting deoxysugar pathways and glycosyltransferases......Page 287 Exploiting oxidoreductases......Page 294 Glossary......Page 299 References......Page 300 Introduction......Page 311 Fatty Acid Biosynthesis and Fatty Acid Synthase......Page 313 The Porcine Type I FAS Structure......Page 314 The Type II PKS......Page 316 Malonyl-Coenzyme A:ACP transacetylase......Page 320 Crystal structure of MAT......Page 322 Proposed molecular basis of substrate specificity of MAT......Page 323 Crystal structure of ZhuH......Page 324 Proposed molecular basis of substrate specificity of ZhuH......Page 326 The Elongating Ketosynthase/Chain Length Factor Complex......Page 327 Proposed mechanism of KS/CLF......Page 328 The Ketoreductase......Page 329 Proposed mechanism of ketoreductase......Page 331 The stereochemistry of ketoreductase......Page 333 The Aromatase/Cyclase......Page 335 Crystal structure of Tcm ARO/CYC......Page 338 Proposed mechanism of Tcm ARO/CYC......Page 340 The Fourth Ring Cyclases......Page 342 Acyl Carrier Protein......Page 344 Protein-Protein Interactions and Transport of Polyketide Intermediates between Enzymes......Page 345 Acknowledgments......Page 346 Abbreviations......Page 347 References......Page 348 Introduction......Page 352 The Chemical Reactions of Fungal Polyketide Biosynthesis......Page 353 Biological Activities......Page 358 Highly Reduced Polyketides......Page 359 The lovastatin polyketide synthases......Page 360 The squalestatin S1 polyketide synthases......Page 361 Highly reduced polyketide synthase from Alternaria solani......Page 362 Partially Reduced Polyketides......Page 364 Nonreduced Polyketides......Page 367 Nonreduced polyketide synthase loading component......Page 368 Nonreduced polyketide synthase chain extension component......Page 370 Chain-shortening reactions......Page 372 C-MeT domains......Page 374 Interaction of isolated NR PKS domains with components of bacterial type II PKS......Page 375 Mixed Polyketide/Nonribosomal Peptides......Page 377 Meroterpenoids......Page 379 Post-PKS Reactions in Fungi......Page 381 Conclusions......Page 383 References......Page 385 Type I Modular PKS......Page 389 Development of the Biosynthetic Theory......Page 390 Synthetic Operations......Page 392 Enzymes of Fatty Acid Biosynthesis......Page 393 Biosynthesis of the Polyketide Chain of Erythromycin......Page 396 Identification of the Megasynthases Involved in Erythromycin Biosynthesis......Page 399 Generation of Truncated Versions of the DEBS......Page 402 Specificity of Transfer of Acyl Group Building Blocks from External CoA Thioesters onto the DEBS Assembly Lines......Page 403 Kinetic Studies of the Structural Specificity of AT Domains......Page 404 Mass Spectrometric Studies of the Structural Specificity of AT Domains......Page 405 Celmer’s Rules......Page 407 Deleting Catalytic Activities......Page 408 Studies of the Stereochemistry of Reactions using Intact Modules and Isotopically Labeled Precursors......Page 409 Studies of the Stereochemistry of Reactions using Reconstructed DEBS Modules......Page 412 Studies of the Quaternary Structure of the Type I FAS......Page 413 Recent Studies of the Type I FAS Structure......Page 414 Mutant complementation studies, leading to the Smith structure for the FAS......Page 415 Direct observations of the complete type I FAS structure by X-ray crystallography: The Ban structure for the animal FAS......Page 416 Comparison of the Smith and Ban Proposals for the Type I FAS Structure......Page 418 Proteolysis Studies on the DEBS Multienzymes......Page 419 NMR Studies of Docking Domains......Page 420 Structures Based on X-ray Images......Page 422 The Cambridge Topology for the PKS Module......Page 423 Other Polyketide Synthases......Page 427 Variation in the Packaging of Modules into Multienzymes......Page 428 Origin of the core structure of monensin......Page 429 The Rapamycin PKS......Page 431 The Mupirocin PKS, an AT-less System with Special Mechanisms for Generating C-1 Branch Points......Page 434 Methymycin and Pikromycin......Page 438 Borrelidin......Page 440 Development of New Versatile Super Hosts and Combinatorial Biosynthesis of Aromatic Compounds by Type II PKS Pathways......Page 442 Creation of hybrid versions of the DEBS......Page 443 Genetic engineering of the chain-extension modules of the DEBS......Page 445 Generation of Analogues of Rapamycin......Page 446 Insertion of a Complete Module into the DEBS Assembly Line......Page 447 Future Perspectives......Page 448 Abbreviations......Page 450 References......Page 451 NRPS/PKS Hybrid Enzymes and Their Natural Products......Page 457 Prototypical Biosynthesis of PK and NRP Natural Products......Page 458 Gene cloning, sequence analysis......Page 462 Isolation and biological activity......Page 465 Gene cloning, sequence analysis......Page 466 Gene cloning, sequence analysis......Page 467 Gene cloning, sequence analysis......Page 468 Isolation and biological activity......Page 469 Gene cloning, sequence analysis......Page 470 Trans-AT Hybrid PKS/NRPS Systems - an Introduction......Page 471 In vitro characterization of trans-AT hybrid PKS/NRPS pathways......Page 472 In vivo biochemistry of trans-AT hybrid PK/NRP......Page 476 PKS/NRPS pathways and in vivo analysis of trans-AT hybrid PK/NRP......Page 477 In vitro biochemical characterization of trans-AT hybrid pathways......Page 478 In vivo biochemistry of trans-AT hybrid PK/NRP......Page 479 Biological activity and structure of trans-AT hybrid PK/NRP......Page 480 PKS/NRPS pathways and in vivo analysis of trans-AT hybrid PK/NRP......Page 481 PKS/NRPS pathways and in vivo analysis of trans-AT hybrid PK/NRP......Page 482 PKS/NRPS pathways and in vivo analysis of trans-AT hybrid PK/NRP......Page 483 PKS/NRPS pathways and in vivo analysis of trans-AT hybrid PK/NRP......Page 484 Overview......Page 485 DNA-Sequencing Strategies in Hybrid PK/NRP Systems......Page 486 Conclusions......Page 487 Abbreviations......Page 488 References......Page 489 Introduction......Page 497 Gene Cluster of the Mevalonate Pathway......Page 498 Archaeal class I HMGR......Page 501 Bacterial class I HMGR......Page 502 Bacterial class II HMGR......Page 504 Class II HMGR as a new molecular target for drug development......Page 505 Two Types of IPP Isomerase......Page 506 Type 1 IPP Isomerase......Page 507 Type 2 IPP Isomerase......Page 510 Biosynthetic Gene Clusters of Secondary Metabolites from Actinomycetes......Page 514 Mevalonate Fermentation......Page 515 Nomenclature......Page 516 References......Page 517 Methylerythritol Phosphate Pathway......Page 521 Formation of Isoprene Units: Mevalonate or Methylerythritol Phosphate Pathway......Page 522 1-Deoxy-d-Xylulose 5-Phosphate and 1-Deoxy-d-Xylulose 5-Phosphate Synthase......Page 526 dxr gene discovery......Page 528 Reaction mechanism......Page 529 Fosmidomycin and fosmidomycin-inspired DXR inhibitors......Page 531 NADPH and substrate analogues......Page 533 From 2-C-Methyl-d-Erythritol 4-Phosphate to 2-C-Methyl-d-Erythritol 2,4-Cyclodiphosphate......Page 534 4-Diphosphocytidyl-2-C-methyl-d-erythritol and 4-diphosphocytidyl-2-C-methyl-d-erythritol synthase......Page 535 4-d-Diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate and 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase......Page 536 2-C-m,ethyl-d-erythritol 2,4-cyclodiphosphate and 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase......Page 537 Bacterial bifunctional 4-diphosphocytidyl-2-C-methyl-d-erythritol synthase/2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase......Page 538 4-Hydroxy-2-Methylbut-2-Enyl Diphosphate and 2-C-Methyl-d-Erythritol 2,4-Cyclodiphosphate Reductase......Page 539 Presence of a branching in the MEP pathway producing IPP and DMAPP......Page 541 4-Hydroxy-2-methylbut-2-enyl diphosphate reductase......Page 542 Higher plants, ferns, and mosses......Page 546 Algae and related nonphototrophic phyla......Page 547 The MEP Pathway: A Target for Antimicrobial Drugs......Page 548 Overproduction of MEP Pathway-Derived Isoprenoids in Bacteria and Plants......Page 549 Isoprenoid Biosynthesis in Plants: MVA Versus MEP Pathway: Cross-Talk between the Cytosolic and the Plastidial Compartments......Page 550 IPP and DMAPP Production in Bacteria and Plants: HMBPP Reductase Versus IPP/DMAPP Isomerase......Page 551 Abbreviations......Page 552 References......Page 553 Introduction......Page 560 Mevalonate Pathway and Nonmevalonate Pathway......Page 561 Biosynthetic Pathway of Isoprenoids Includes Various Prenyltransferases......Page 562 Short-chain (E)-prenyltransferases......Page 564 Medium-chain (E)-prenyltransferases......Page 565 Stereochemistry of (E)-Prenyltransferases......Page 566 FPP synthase......Page 567 Roles of conserved amino acid residues......Page 568 Product Chain-Length Regulation Mechanism......Page 571 (Z)-Prenyl Diphosphate Synthases......Page 572 Short- and long-chain (Z)-prenyltransferases......Page 574 Three-Dimensional Structure of (Z)-Prenyltransferase......Page 575 Catalytic Mechanism......Page 577 Product Chain-Length Regulation Mechanism......Page 580 Conclusions......Page 582 References......Page 583 Introduction......Page 587 Monoterpene Cyclase Enzymology......Page 590 Ionization and Isomerization of Geranyl Diphosphate......Page 592 Cyclization Reaction Stereochemistry......Page 593 Formation of Monoterpene Structural Types......Page 595 Molecular Biology of the Monoterpene Cyclases......Page 596 Structural Commonalities......Page 597 (-)-(4S)-Limonene Synthase......Page 600 (+)-Bornyl Diphosphate Synthase......Page 602 1,8-Cineole Synthase......Page 605 Acknowledgments......Page 607 References......Page 608 Introduction......Page 611 Carotenoid Cleavage Products......Page 612 Farnesanes......Page 613 Drimanes......Page 615 Cyclic Sesquiterpenes......Page 616 The bisabolane series......Page 619 The cuparane series......Page 621 The cadinane series......Page 624 The humulane series......Page 626 The germacrane series......Page 628 Decorating the Sesquiterpene Scaffolds......Page 632 Future Challenges......Page 637 Glossary......Page 638 References......Page 639 Introduction......Page 644 Formation of Four Copalyl Diphosphate Stereoisomers......Page 645 Diterpene resin acids in conifers......Page 647 Phyllocladane-related diterpenes in a fungus......Page 648 ent-Labdane-related diterpenes in rice......Page 651 ent-Pimarane-related diterpenes in eubacteria......Page 653 Gibberellins......Page 654 syn-Labdane-related diterpenes in rice......Page 657 Aphidicolane-related diterpenes in a fungus......Page 660 Clerodane......Page 661 Halimane......Page 662 Taxane and Phomactane......Page 663 Casbene and Cembratriene......Page 664 Fusicoccane......Page 666 Summary and Future Prospects......Page 669 References......Page 670 Introduction......Page 674 Cyclization Mechanism......Page 675 Mechanism......Page 677 Genes......Page 680 Mutational Studies......Page 681 Structure of Human Lanosterol Synthase......Page 682 Mechanism......Page 685 Genes......Page 686 Product specificity......Page 688 Multifunctional Triterpene Synthase......Page 689 Arabidopsis Triterpene Synthases......Page 692 Isomultiflorenol synthase......Page 696 Cucurbitadienol synthase......Page 697 Baccharis oxide synthase......Page 700 Squalene cyclases from ferns......Page 701 Triterpene Tailoring Steps......Page 702 Summary and Future Perspectives......Page 705 References......Page 706 Introduction......Page 710 The Reaction Mechanism......Page 712 The Enzyme Structure......Page 713 Residues for Initiation and Termination......Page 717 Residues for Cation Stabilization......Page 718 Squalene and Oxidosqualene......Page 720 Analogues with Various Chain Lengths......Page 721 Heteroaromatic Ring-Containing Analogues......Page 723 Methylidene-Extended Analogues......Page 725 Fluorine and Sulfur Analogues......Page 727 Desmethylsqualenes and Other Analogues......Page 728 Conclusions......Page 730 References......Page 731 Introduction......Page 734 Biosynthesis of Basic Structures of Carotenoids......Page 735 Photosynthetic Bacteria......Page 737 Nonphotosynthetic Bacteria - Genus Pantoea......Page 738 Nonphotosynthetic Bacteria - Genera Paracoccus and Brevundimonas......Page 740 Cyanobacteria......Page 743 Pathway Engineering for Increasing the Intracellular Concentration of Farnesyl Diphosphate......Page 746 Biosynthesis of Carotenoids in Higher Plants......Page 747 Pathway Engineering for the Production of Ketocarotenoids in Higher Plants......Page 750 References......Page 751 Introduction......Page 755 Squalene or 2,3-oxidosqualene cyclizations......Page 756 2,3-Oxidosqualene cyclization in cycloartenol or lanosterol in eukaryotes......Page 757 Metabolization of the cyclopropane ring of 9beta,19-cyclopropyl sterols......Page 758 Sterol-C24-methyltransferases......Page 759 Sterol-22-desaturase......Page 762 The C4-demethylation complex......Page 763 CYP51......Page 764 A common trunk of genes implicated in isomerization, desaturation, and reductions on the B and D rings......Page 766 Steroidal hormones in fungi......Page 768 Brassinosteroids......Page 769 Steroidal saponins......Page 771 Steroidal glycoalkaloids......Page 772 Cardiotonic steroidal glucosides......Page 773 Steryl Esters......Page 774 Steroid Sulfates......Page 775 Transport......Page 776 Molecular Regulation of Sterol Biosynthesis......Page 777 Functions of Steroids......Page 778 Abbreviations......Page 779 References......Page 780 Introduction......Page 788 Cyclic Monoterpene......Page 789 Cyclic Sesquiterpene......Page 790 Cyclic Diterpene......Page 795 Other Cyclic Isoprenoids......Page 798 Hybrid Isoprenoids......Page 800 Polyketide-Isoprenoid Hybrid Compound......Page 801 Moenomycin A/Pholipomycin/AC326-Alpha......Page 804 Phenazine-Isoprenoid Hybrid Compounds......Page 805 Other Isoprenoid Hybrid Compounds......Page 806 References......Page 810 Lignans (Neolignans) and Allyl/Propenyl Phenols: Biogenesis, Structural Biology, and Biological/Human Health Considerations......Page 814 Introduction......Page 816 Inconsistencies in Current Nomenclature of Lignans and Neolignans......Page 817 Algae......Page 820 Bryophytes: liverworts, hornworts, and mosses......Page 824 Gymnosperms......Page 825 Angiosperms......Page 826 Bryophytes: liverworts, hornworts, and mosses......Page 829 Pteridophytes: lycophytes, horsetails, and ferns......Page 832 Gymnosperms......Page 835 Angiosperms......Page 839 Evolution of Biochemical Pathways to Allyl-/Propenylphenols and Lignans: Observations on Co-occurrence......Page 844 Discovery of the (+)-Pinoresinol-Forming Dirigent Protein and Encoding Gene......Page 846 Discovery of the (-)-Pinoresinol-Forming Dirigent Protein and Encoding Gene......Page 848 mRNA tissue localization......Page 850 Dirigent protein tissue localization and proposed proteins harboring arrays of dirigent sites......Page 851 Western red cedar......Page 852 Arabidopsis......Page 853 Other Examples of 8-8’ Phenylpropanoid Coupling: Hydroxycinnamic Acid and Allyl-/Propenylphenol-Derived Lignans in Liverworts and the Creosote Bush......Page 854 Methylenedioxy bridge formation......Page 855 Glucosylation......Page 858 Forsythia PLR: discovery of (+)-pinoresinol/lariciresinol reductase......Page 859 Linum species PLR: additional discovery of genes encoding (-)-PLR activity......Page 861 Arabidopsis PLR homologs: Pinoresinol reductases......Page 864 In situ hybridization of Forsythia PLR: Comparison with DP gene expression......Page 865 Stereospecificity of hydride transfer with resulting inversion of product configuration......Page 866 Structural biology/substrate versatility studies......Page 867 PLR and PLR homolog enantiospecificity......Page 869 Discovery of SDH and encoding gene......Page 872 Structural biology studies......Page 873 Hinokinin......Page 875 Podophyllotoxin/6-Methoxypodophyllotoxin......Page 876 Other Phenylpropanoid Coupling Modes: 8-2’, 8-3’ (8-5’), and 8-O-4’-Linked Lignans......Page 877 8-3’ (8-5’) Coupling......Page 878 Allylic (Phenylpropenal) Double Bond Reductases: Biosynthesis of Dihydrolignans and Dihydromonolignols......Page 879 Discovery of allylic (phenylpropenal) double bond reductases and gene cloning: Loblolly pine (Pinus taeda)......Page 881 Allylic double bond reductase homologs: eleven-membered multigene family in Arabidopsis......Page 882 Structural biology studies: Arabidopsis DBR1......Page 883 PLR Homologs: Phenylcoumaran Benzylic Ether Reductases, Isoflavone Reductases, and Pterocarpan Reductases......Page 886 Structural biology studies of PLR homologs: PCBER, IFR, and pterocarpan reductases......Page 887 Hinokiresinol: Discovery of Biochemical Pathway, Encoding Genes, and Enzymes......Page 888 Acetylenic Norlignans......Page 890 Allyl-/Propenylphenol Biosynthesis......Page 891 Radiolabel tracer studies: controversy over intact incorporation of monolignol pathway intermediates and scientific judgment?......Page 892 Intermediacy of monolignol esters in allyl-/propenylphenol biosynthesis: clues from norlignans?......Page 894 Creosote bush chavicol/eugenol synthase (CES)......Page 897 Piper regnellii......Page 898 Chemotaxonomy, kinetic properties, and homology comparisons of CES/AIS with PCBER, PLR, IFR (-like) annotations in the plant kingdom: caveats on incomplete analyses......Page 899 Pinus taeda......Page 900 CES (AIS) structural and mechanistic studies: comparison to PLRs, PCBERs, and IFRs......Page 902 Allyl-/propenylphenol downstream metabolism......Page 903 Monolignol Acyltransferases: Incomplete Characterization and Substrate Degeneracy......Page 904 Biological Properties in Planta and in Human Usage......Page 905 Antimicrobial properties......Page 906 Mutagenicity......Page 907 Podophyllotoxin and derivatives......Page 908 Enterolignans and cancer prevention......Page 910 Other lignans and norlignans with anticancer potential......Page 911 Nutraceutical lignans: sesame......Page 912 Properties in planta......Page 914 References......Page 915 Introduction......Page 928 Brief Overview of Phenylpropanoid Research in the Past 10 Years......Page 929 Phenylpropene Synthase and O-Methyltransferases Involved in Flavor and Scent Biosynthesis......Page 930 Curcuminoid Synthase......Page 932 Scopoletin biosynthesis in Arabidopsis thaliana: Identification of feruloyl-CoA 6’-hydroxylase as a 2-oxoglutarate-dependent dioxygenase......Page 933 Furanocoumarin biosynthesis: Identification of psoralen synthase......Page 934 Daphnetin 8-O-methyltransferase......Page 935 Chalcones......Page 936 6’-Deoxychalcone......Page 937 Glycosylation of chalcones......Page 938 Aurones......Page 939 Chalcone Isomerase and Flavanones......Page 940 Cytochrome P-450s responsible for flavone formation (flavanone 2-hydroxylase and flavone synthase II)......Page 942 Anthocyanidin synthase (synonym of leucoanthocyanidin dioxygenase)......Page 944 Reductases......Page 945 Flavonoid 3’-hydroxylase and flavonoid 3’,5’-hydroxylase......Page 947 Other hydroxylases of flavonoid skeleton......Page 949 O-Methyltransferases......Page 950 Glucosyltransferases......Page 951 Galactosyltransferases......Page 953 Hydroxycinnamoyl-CoA: anthocyanidin 3-O-glucoside-6Prime-O-hydroxycinnamoyltransferase......Page 954 Molecular genetic and functional genomic approaches to anthocyanin acyltransferases from A. thaliana......Page 955 Isoflavonoids......Page 956 Biosynthesis of isoflavones in leguminous plants......Page 957 2-Hydroxyisoflavanone dehydratase......Page 958 2-Hydroxyisoflavanone 4’-O-methyltransferase......Page 959 Glycosyltransferase......Page 960 Biosynthesis of pterocarpan and isoflavan skeletons......Page 961 Isoflavone 2’- and 3’-hydroxylases......Page 962 Pisatin biosynthesis in pea......Page 963 Metabolomics and Transcriptomics......Page 965 Evolution of Phenylpropanoid/Flavonoid Biosynthesis......Page 966 References......Page 967 Classes of Alkaloids......Page 976 Function and Diversity of Alkaloids......Page 977 Strategies for Elucidating Alkaloid Biosynthesis......Page 981 Benzylisoquinoline Alkaloid Biosynthesis......Page 986 Monoterpene Indole Alkaloid Biosynthesis......Page 991 Tropane Alkaloid Biosynthesis......Page 998 Conclusions and Outlook......Page 1000 References......Page 1002

This work presents a definitive interpretation of the current status of and future trends in natural products-a dynamic field at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids, and enzymes. With more than 1,800 color figures, Comprehensive Natural Products II features 100% new material and complements rather than replaces the original work (©1999).

• Reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine
• Stimulates new ideas among the established natural products research community-which includes chemists, biochemists, biologists, botanists, and pharmacologists
• Informs and inspires students and newcomers to the field with accessible content in a range of delivery formats
• Includes 100% new content, with more than 6,000 figures (1/3 of these in color) and 40,000 references to the primary literature, for a thorough examination of the field
• Highlights new research and innovations concerning living organisms and their distinctive role in our understanding and improvement of human health, genomics, ecology/environment, and more
• Adds to the rich body of work that is the first edition, which will be available for the first time in a convenient online format giving researchers complete access to authoritative Natural Products content