Comprehensive Natural Products II: Chemistry and Biology: Cofactors Volume 7

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 15 GTP Cyclohydrolase II......Page 16 Deaminase/Reductase......Page 20 3,4-Dihydroxy-2-Butanone 4-Phosphate Synthase......Page 23 Lumazine Synthase......Page 24 Riboflavin Synthase......Page 27 Pentameric Riboflavin Synthases of Archaea......Page 34 Regulation of Riboflavin Biosynthesis......Page 35 Riboflavin Biosynthesis Genes as Potential Drug Targets......Page 40 Riboflavin as Substrate for Other Biosynthetic Pathways......Page 41 References......Page 44 Flavin-Dependent Enzymes......Page 49 Introduction......Page 50 Oxidation of Carbon-Heteroatom Bonds......Page 54 d-Amino acid oxidase......Page 55 Monoamine oxidase......Page 57 Monomeric sarcosine oxidase......Page 60 Proline dehydrogenases......Page 61 Pyridine nucleotide oxidations......Page 62 Glucose oxidase......Page 63 Flavocytochrome b2......Page 64 Lactate monooxygenase......Page 66 Prenylcysteine lyase......Page 67 Old Yellow Enzyme......Page 68 Acyl-CoA Dehydrogenases and Oxidases......Page 70 Dihydroorotate dehydrogenase......Page 72 Dihydropyrimidine dehydrogenase......Page 74 Succinate Dehydrogenase and Fumarate Reductase......Page 75 UDP-N-acetylenolpyruvylglucosamine reductase......Page 76 Glutathione Reductase......Page 77 Thioredoxin Reductase......Page 79 Lipoamide Dehydrogenase......Page 80 Mercuric Reductase......Page 82 Electron Transfer Reactions......Page 84 Electron-Transferring Flavoproteins......Page 85 Phthalate Dioxygenase Reductase......Page 86 Cytochromes P-450 Reductase......Page 87 Oxygen Reactions......Page 88 Reaction of Free Flavins with O2......Page 89 Oxidases......Page 90 p-Hydroxybenzoate Hydroxylase......Page 91 MICAL......Page 93 Tryptophan-7-Halogenase......Page 94 ActVA and ActVB......Page 95 Flavin-Containing Monooxygenase......Page 96 Baeyer-Villiger Monooxygenases......Page 97 Bacterial Luciferase......Page 98 Alkyldihydroxyacetonephosphate Synthase......Page 99 UDP-Galactopyranose Mutase......Page 100 Chorismate Synthase......Page 102 Oxynitrilase......Page 106 Acetohydroxyacid Synthase......Page 107 Glutamate Synthase......Page 108 Aclacinomycin Oxidoreductase......Page 110 Berberine Bridge Enzyme......Page 111 2-Aminobenzyl-CoA Monooxygenase/Reductase......Page 112 Abbreviations......Page 113 References......Page 115 Scope......Page 126 Introduction......Page 127 Chemical Riboflavin Synthesis......Page 128 Microbial Riboflavin Production......Page 130 Fungi......Page 131 Bacteria......Page 133 Bacillus subtilis and Ashbya gossypii as Preferred Host Strains......Page 134 Bacillus subtilis production strains: rib genes driven by their natural promoters......Page 135 Bacillus subtilis production strains: rib gene expression driven by heterologous promoters......Page 136 Corynebacterium ammoniagenes......Page 137 Purine and guanosine pathway, nitrogen metabolism in Bacillus subtilis......Page 138 Pentose phosphate pathway......Page 139 Modifications in the central metabolism of Bacillus subtilis production strains......Page 140 Riboflavin Transmembrane Transport......Page 141 Classical Strain Improvement and Whole Genome Sequencing......Page 142 Glucose and Biotin-Limited Fed-Batch Fermentation Process for Bacillus subtilis Production Strains......Page 143 Product Isolation and Purification......Page 144 Conclusions......Page 146 References......Page 147 The Goal......Page 151 More Precisely, What Is a Subsystem?......Page 153 How Are Subsystems Built?......Page 160 What Is Revealed by the Construction of Subsystems?......Page 164 Summary......Page 165 References......Page 166 The Biosynthetic Pathway......Page 170 The origin of pimelate......Page 172 Characterization of the enzyme......Page 174 Search for inhibitors......Page 177 Characterization of the enzyme......Page 178 Search for inhibitors......Page 179 Characterization of the enzyme......Page 180 Search for inhibitors......Page 182 Characterization of the enzyme and mechanistic studies......Page 183 Regulation of the Pathway......Page 186 References......Page 187 Properties of Lipoic Acid......Page 190 Discovery of Lipoamide......Page 192 The alpha-Keto Acid Dehydrogenase Complexes......Page 193 The Glycine Cleavage System......Page 197 Lipoamide Dehydrogenase......Page 198 Pathways for Construction of the Lipoyl Cofactor......Page 199 Lipoate Protein Ligase A......Page 202 Lipoate-Activating Enzyme......Page 204 Octanoyl-[Acyl Carrier Protein]-Protein Transferase......Page 205 Metabolic feeding studies......Page 207 Isolation and characterization......Page 209 Mechanistic studies of LipA......Page 212 Acknowledgment......Page 215 References......Page 217 Introduction......Page 222 Biochemical Transformations and Enzymes......Page 223 Synthesis of Quinolinate......Page 227 l-Aspartate oxidase......Page 228 l-Aspartate dehydrogenase......Page 229 Kynurenine pathway......Page 230 Kynurenine formamidase......Page 232 Kynurenine 3-monooxygenase (KYNMO)......Page 233 3-Hydroxyanthranilate 3,4-dioxygenase......Page 234 Pyridine Mononucleotides......Page 235 Nicotinate phosphoribosyltransferase......Page 236 The nicotinamide phosphoribosyltransferase......Page 237 NMN deamidase......Page 238 Ribosyl nicotinamide kinase......Page 239 Ribosyl nicotinamide phosphorylase......Page 241 Formation of Pyridine Dinucleotides......Page 242 NMN adenylyltransferase of the NadR family in bacteria......Page 243 NaMN- and NMN-specific adenylyltransferases of the NadM family in bacteria and archaea......Page 244 NaMN- and NMN-specific adenylyltransferases in eukaryotes......Page 245 Amidation of Pyridine Nucleotides......Page 246 NAD synthetase......Page 247 NMN synthetase......Page 248 NAD kinase......Page 249 Biosynthetic pathways......Page 250 Transcriptional regulation......Page 253 NadR family......Page 254 Archaea......Page 255 Eukaryota......Page 257 Abbreviations......Page 259 References......Page 260 Introduction......Page 267 Enzymology of PLP Biosynthesis via the DXP-Dependent Route......Page 268 Enzymology of PLP Biosynthesis via the R5P-Dependent Route......Page 273 Transport, Salvage, and Interconversion of Various Forms of Vitamin B6......Page 275 Abbreviations......Page 276 References......Page 277 Pyridoxal 5’-Phosphate-Dependent Enzymes: Catalysis, Conformation, and Genomics......Page 281 From Vitamin B6 to Pyridoxal 5’-Phosphate......Page 282 Overview of PLP Catalysis......Page 283 Dunathan’s hypothesis......Page 286 Families of PLP-Enzymes Based on Evolutionary Relationships and Fold Types of PLP-Enzymes Based on Three-Dimensional Structures......Page 287 Alanine racemase......Page 288 Decarboxylation......Page 290 Ornithine decarboxylase......Page 292 DOPA decarboxylase......Page 293 alpha-Elimination and alpha-Replacement Reactions......Page 294 Serine hydroxymethyltransferase......Page 295 Threonine aldolase......Page 297 1-Aminocyclopropane-1-carboxylate deaminase......Page 298 Aminotransferases......Page 299 Tyrosine phenol-lyase......Page 303 Cystalysin......Page 306 Cysteine desulfurases......Page 307 Cystathionine beta-lyase......Page 308 beta-Replacement Reactions......Page 309 Tryptophan synthase......Page 310 O-acetylserine sulfhydrylase......Page 312 Cystathionine beta-synthase......Page 313 Cystathionine gamma-lyase......Page 314 Threonine synthase......Page 316 Cystathionine gamma-synthase......Page 317 Lysine 2,3-aminomutase......Page 320 Reactivity with Inhibitors......Page 323 Activated electrophiles......Page 325 Aromatization mechanism-based inhibitors......Page 326 Noncovalent inhibitors......Page 333 Coenzyme-substrate analogues......Page 334 Aspartate Aminotransferase and the Open/Closed Transition in PLP-Dependent Enzymes......Page 335 Tryptophan Synthase......Page 336 How Old is PLP?......Page 337 How Did PLP-Dependent Enzymes Emerge and Evolve?......Page 338 A Case Study: Fold-Type I Enzymes......Page 340 Exploring the Modern PLP-Dependent Enzymes: Can Sequence be Used to Infer Function?......Page 341 Abbreviations......Page 344 References......Page 345 Coenzyme A Biosynthesis and Enzymology......Page 359 Introduction......Page 360 Discovery and Early Studies of CoA and CoA Enzymology......Page 361 Early Studies of CoA Biosynthesis......Page 362 CoA Biosynthesis......Page 363 Pantothenate (and Pantetheine) Transport......Page 365 Type I pantothenate kinases......Page 366 Type II pantothenate kinases......Page 367 Type III pantothenate kinases......Page 368 Archaeal pantothenate kinases......Page 369 Distribution of PanK types......Page 370 Pantothenate kinase as a salvage enzyme......Page 371 PPCS (coaB Gene Product)......Page 372 Phosphopantothenoylcysteine Decarboxylase (coaC Gene Product)......Page 374 Phosphopantetheine Adenylyltransferase (coaD Gene Product)......Page 377 Dephospho-Coenzyme A Kinase (coaE Gene Product)......Page 379 Genomic Variations in the CoA Biosynthetic Pathway......Page 380 Phosphopantetheinyl transferase/ACP synthase......Page 382 Triphosphoribosyl-dephospho-CoA formation and utilization......Page 385 CoA diphosphatases......Page 386 Pantetheinase......Page 387 CoA disulfide reductase......Page 388 Ligases: Coupling activated carboxylic acids to CoA directly......Page 390 Oxidoreductases: CoA thioester formation through oxidative decarboxylation of alpha-keto acids......Page 392 Nitrogen- and oxygen-based acceptors (N- and O-acyltransferases)......Page 393 Acyl exchange reactions (CoA-transferases)......Page 396 Water as acceptor (thioesterases)......Page 398 Acyl-CoAs (or acyl-ACPs) as electrophiles: True Claisen condensations (thiolases)......Page 399 Ketones, aldehydes, and carboxylates as electrophiles......Page 400 Lyases: Using CoA to Break Carbon-Carbon bonds......Page 403 Chemical Biology Tools Based on CoA Enzymology......Page 404 Preparation of CoA Analogues......Page 405 CoA analogues as reporter labels......Page 407 Drug Development Efforts Targeting CoA Enzymology......Page 410 References......Page 411 Introduction......Page 419 o-Succinylbenzoate Pathway......Page 422 Formation of isochorismate (compound (4)rarr(5))......Page 423 Formation of succinic semialdehyde-thiamine pyrophosphate anion and Michael addition to isochorismate (compound (5)+(13)rarr(14))......Page 426 The aromatization of SHCHCrarrOSB (compound (15)rarr(7))......Page 427 Cyclization of OSB to DH2NA (compound (7)rarr(18))......Page 428 Methylation of DMK to MK (compound (3)rarr(2))......Page 429 Non-o-Succinylbenzoate or Futalosine Pathway......Page 430 Phylloquinone Biosynthesis......Page 433 Ubiquinone Biosynthesis......Page 434 The Conversion of Chorismate to 4-HB by the CPL (Compound (4)rarr(11))......Page 437 Tyrosine-4-Hydroxyphenylpyruvate Pathway (Compound (12)rarr(10))......Page 438 Prenylation of 4-Hydroxybenzoate (Compound (11)rarr(49))......Page 439 Formation of 2-Octaprenylphenol (Compound (49)rarr(50))......Page 440 Hydroxylation reactions......Page 441 Methylation reactions......Page 442 Comparison of Q Biosynthesis in Yeast and Escherichia coli......Page 444 Abbreviation......Page 447 References......Page 448 Biosynthesis of Heme and Vitamin B12......Page 453 Tetrapyrrole Biosynthetic Pathways......Page 454 5-Aminolevulinic Acid Synthase......Page 456 Glutamyl-tRNA Reductase and Glutamate-1-Semialdehyde-2,1-Aminomutase......Page 457 Porphobilinogen Synthase......Page 461 Uroporphyrinogen III Synthase......Page 464 Uroporphyrinogen III Decarboxylase......Page 467 Coproporphyrinogen III Oxidase......Page 470 Ferrochelatase......Page 471 A Note on Nomenclature......Page 473 Uroporphyrinogen III to Precorrin-2......Page 477 Precorrin-3B Synthesis......Page 482 Precorrin-4 Synthesis, Ring Contraction, and C17 Methylation......Page 484 Precorrin-8 Synthesis, Methylation at C5, C15, and Decarboxylation......Page 485 Hydrogenobyrinic Acid Synthesis......Page 486 Cobalt Reduction......Page 487 Adenosylation......Page 488 Cobalt Insertion......Page 489 Methylation at C20......Page 491 Methylation at C1......Page 492 Amidation of the Macrocycle......Page 493 Attachment of (R)-1-Amino-2-Propanol O-2-Phosphate......Page 494 Synthesis of 5,6-Dimethylbenzimidazole......Page 497 Synthesis of alpha-Ribazole......Page 499 Synthesis of Adenosylcobalamin......Page 500 References......Page 501 Cobalamin Coenzymes in Enzymology......Page 508 Introduction......Page 509 Enzymatic Reactions of Adenosylcobalamin (Coenzyme B12)......Page 510 Methylcobalamin......Page 512 Chemical Reactions......Page 513 Reactions of Alkylcobalamins......Page 514 Stereochemistry......Page 516 Hydrogen transfer by adenosylcobalamin......Page 518 A free radical intermediate......Page 519 Subunit composition and structure......Page 521 Spanning the distance......Page 522 The roles of K+......Page 523 Isomerization mechanism......Page 524 Ethanolamine Ammonia-Lyase......Page 525 Participation of coenzyme B12 in hydrogen transfer......Page 526 Radical intermediates......Page 527 Reaction mechanism......Page 528 Lysine 5,6-Aminomutase......Page 530 Molecular structure......Page 531 Suicide inactivation by substrates......Page 532 Reaction and molecular composition......Page 534 The radical mechanism of methylmalonyl-CoA mutase......Page 535 Cleavage of the Co-C5’ bond......Page 537 Function of adenosylcobalamin......Page 538 Molecular properties and structure......Page 539 Reaction mechanism......Page 541 Discovery and properties......Page 542 Reaction mechanism......Page 543 Reaction mechanism......Page 545 Modular function......Page 546 Conclusion......Page 547 Abbreviations......Page 548 References......Page 549 Thiamin Biosynthesis in Bacillus subtilis......Page 554 Thiamin Phosphate Synthase......Page 555 Biosynthesis of the Thiazole Moiety of Thiamin in Bacteria......Page 556 Protein Thiocarboxylates as Sulfide Carriers in Thiamin Biosynthesis......Page 557 Formation of the Pyrimidine Moiety of Thiamin......Page 558 Thiamin Salvage......Page 560 Chemoenzymatic Synthesis of Thiamin Pyrophosphate......Page 561 Formation of the Thiamin Thiazole in Yeast......Page 562 Conclusions......Page 563 References......Page 564 Thiamin Enzymology......Page 567 Thiamin Diphosphate-Related Intermediates Prior to Substrate Addition......Page 568 The 1’,4’-iminopyrimidine form of thiamin diphosphate31-35......Page 573 Determination of pKa for the enzyme-bound APH+ form35......Page 574 The Michaelis-Menten complex......Page 575 Observation of the intermediate analogs derived from substrate analog phosphonates and phosphinates......Page 576 Observation of LThDP analogs from chromophoric substrate analogs......Page 578 The first postdecarboxylation intermediate: The enamine/C2alpha-carbanion......Page 581 Evidence on YPDC......Page 582 2-Acetylthiamin diphosphate, the two-electron oxidation product of the enamine......Page 583 The C2alpha-hydroxyethylideneThDP radical, the one-electron oxidation product of the enamine......Page 584 Determination of Rate-Limiting Steps and Microscopic Rate Constants on ThDP Enzymes......Page 585 Evidence on YPDC......Page 586 Structural evidence pointing to mobile loops......Page 588 Studies on the inner active center mobile loop of E1ec46,99,100......Page 590 Structural Evidence......Page 593 The amino terminal region of E1ec interacts with E2ec......Page 594 Region of E2ec interacting with E1ec......Page 595 The Proton Wire Mechanism......Page 596 Kinetic Evidence for Nonequivalence of Active Sites......Page 597 Evidence from Solvent Effects on Decarboxylation Rate Constants in Model Compounds......Page 599 Perspective for Future Studies......Page 600 References......Page 601 The Biosynthesis of Folate and Pterins and Their Enzymology......Page 605 Introduction......Page 606 Tetrahydrofolate derivatives......Page 608 Biosynthesis of Tetrahydrofolate......Page 609 4-Amino-4-deoxychorismate synthase (EC 6.3.5.8)......Page 611 Guanosine triphosphate cyclohydrolase I (EC 3.5.4.16)......Page 612 Dephosphorylation of dihydroneopterin triphosphate......Page 613 6-Hydroxymethyl-dihydropterin pyrophosphokinase (EC 2.7.6.3)......Page 615 Dihydropteroate synthase (EC 2.5.1.15)......Page 616 Dihydrofolate reductase (EC 1.5.1.3)......Page 617 Dihydropteroate reductase......Page 618 Tetrahydrofolate Enzymes as Drug Targets......Page 619 Cofactor-dependent enzyme systems......Page 622 Cellular and systemic functions of BH4......Page 625 Reaction mechanism of the de novo pathway......Page 626 6-Pyruvoyl tetrahydropterin synthase (PTPS)......Page 627 Alternative routes for biosynthesis of BH4......Page 629 Regeneration of BH4......Page 630 Pterin-4a-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1a......Page 631 Tetrahydrobiopterin in Disease......Page 633 An Introduction to Molybdopterin Biosynthesis and Molybdoenzymes......Page 634 The enzymology of Rhodobacter capsulatus xanthine dehydrogenase (XDH)......Page 636 Conversion of guanosine monophosphate to precursor Z......Page 638 Insertion of sulfur into precursor Z and formation of molybdopterin......Page 639 Insertion of molybdenum into molybdopterin......Page 641 Attachment of guanosine monophosphate......Page 642 Chaperones for the insertion and targeting of bis-molybdopterin guanine dinucleotide and sulfurated molybdenum cofactor into prokaryotic molybdoenzymes......Page 643 Molybdenum cofactor deficiency and isolated sulfate oxidase deficiency......Page 644 Abbreviations......Page 645 References......Page 647 Vitamin B6 Catabolism......Page 655 Heme Catabolism......Page 658 Vitamin B3 Catabolism......Page 663 Vitamin B9, Folate Catabolism......Page 665 Vitamin B7, Biotin Catabolism......Page 668 Conclusion......Page 669 Acknowledgment......Page 671 Abbreviations......Page 675 References......Page 676 Introduction......Page 681 Pyruvoyl Cofactor Biosynthesis......Page 683 Pyruvoyl Cofactor-Dependent Catalysis......Page 684 MIO Biosynthesis......Page 686 MIO-Dependent Catalysis......Page 687 Topaquinone......Page 688 TPQ biosynthesis......Page 689 TPQ-dependent catalysis......Page 691 LTQ-dependent catalysis......Page 692 TTQ biosynthesis......Page 694 TTQ-dependent catalysis......Page 695 Cysteine Tryptophylquinone......Page 696 CTQ-dependent catalysis......Page 699 Galactose oxidase cofactor biosynthesis......Page 701 Galactose oxidase cofactor-dependent catalysis......Page 702 KatG cofactor biosynthesis......Page 703 Cross-Linked Amino Acid Residues in Complex Copper Enzymes......Page 704 Related Fluorescent Protein Fluorophores......Page 707 PQQ Biosynthesis......Page 709 PQQ-Dependent Catalysis......Page 710 Lantibiotics, Protein-Derived Antibiotic Peptides......Page 712 Abbreviations......Page 713 References......Page 714 Introduction......Page 717 Tyrosine Decarboxylase......Page 718 Biosynthesis of Meso-1,3,4,6-Hexanetetracarboxylic Acid......Page 720 Introduction......Page 722 Biosynthesis of 4-Aminobenzoic Acid......Page 724 Formation of 4-(beta-d-Ribofuranosyl)Aminobenzene-5’-Phosphate......Page 725 Reduction of Dihydromethanopterin......Page 728 Early Steps in F420 and Riboflavin Biosynthetic Pathways Leading to 5-Amino-6-Ribitylamino-2,4(1H,3H)-Pyrimidinedione......Page 730 Biosynthesis of 7,8-Didemethyl-8-Hydroxy-5-Deazariboflavin......Page 731 Assembly of the Side Chains of the Core Structure of the F420 Coenzyme F420-0......Page 732 Assembly of the Core Structure of F420 Coenzymes......Page 734 Biosynthesis of Riboflavin, FMN, and FAD......Page 736 Biosynthesis of Coenzyme M......Page 741 Biosynthesis of Coenzyme B......Page 743 Formation of the Coenzyme M and Coenzyme B Thiols......Page 744 Formation of 1-Amino-2-Propanol......Page 746 Formation of the Benzimidazole Moiety......Page 748 Biosynthesis of Coenzyme F430......Page 749 References......Page 751

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