ENTRY map04750 Pathway NAME Inflammatory mediator regulation of TRP channels DESCRIPTION The TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive dorsal root ganglion (DRG) neuron cell bodies including their peripheral and central projections. These channels can be modulated indirectly by inflammatory mediators such as PGE2, bradykinin, ATP, NGF, and proinflammatory cytokines that are generated during tissue injury. While the noxious heat receptor TRPV1 is sensitized (that is, their excitability can be increased) by post-translational modifications upon activation of G-protein coupled receptors (GPCRs) or tyrosine kinase receptors, the receptors for inflammatory mediators, the same action appears to mainly desensitize TRPM8, the main somatic innocuous cold sensor. This aforementioned sensitization could allow the receptor to become active at body temperature, so it not only contributes toward thermal hypersensitivity but also is possibly a substrate for ongoing persistent pain. CLASS Organismal Systems; Sensory system PATHWAY_MAP map04750 Inflammatory mediator regulation of TRP channels DBLINKS GO: 0019233 REFERENCE PMID:15820689 AUTHORS Wang H, Woolf CJ TITLE Pain TRPs. JOURNAL Neuron 46:9-12 (2005) DOI:10.1016/j.neuron.2005.03.011 REFERENCE PMID:17321113 AUTHORS Levine JD, Alessandri-Haber N TITLE TRP channels: targets for the relief of pain. JOURNAL Biochim Biophys Acta 1772:989-1003 (2007) DOI:10.1016/j.bbadis.2007.01.008 REFERENCE PMID:18427980 AUTHORS Cheng JK, Ji RR TITLE Intracellular signaling in primary sensory neurons and persistent pain. JOURNAL Neurochem Res 33:1970-8 (2008) DOI:10.1007/s11064-008-9711-z REFERENCE PMID:24099085 AUTHORS Julius D TITLE TRP channels and pain. JOURNAL Annu Rev Cell Dev Biol 29:355-84 (2013) DOI:10.1146/annurev-cellbio-101011-155833 REFERENCE PMID:12838328 AUTHORS Patapoutian A, Peier AM, Story GM, Viswanath V TITLE ThermoTRP channels and beyond: mechanisms of temperature sensation. JOURNAL Nat Rev Neurosci 4:529-39 (2003) DOI:10.1038/nrn1141 REFERENCE PMID:16776582 AUTHORS Dhaka A, Viswanath V, Patapoutian A TITLE Trp ion channels and temperature sensation. JOURNAL Annu Rev Neurosci 29:135-61 (2006) DOI:10.1146/annurev.neuro.29.051605.112958 REFERENCE PMID:18615141 AUTHORS Story GM TITLE The emerging role of TRP channels in mechanisms of temperature and pain sensation. JOURNAL Curr Neuropharmacol 4:183-96 (2006) DOI:10.2174/157015906778019482 REFERENCE PMID:17548207 AUTHORS Velazquez KT, Mohammad H, Sweitzer SM TITLE Protein kinase C in pain: involvement of multiple isoforms. JOURNAL Pharmacol Res 55:578-89 (2007) DOI:10.1016/j.phrs.2007.04.006 REFERENCE PMID:16319926 AUTHORS Zhang X, Huang J, McNaughton PA TITLE NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. JOURNAL EMBO J 24:4211-23 (2005) DOI:10.1038/sj.emboj.7600893 REFERENCE PMID:19074743 AUTHORS Bessac BF, Jordt SE TITLE Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. JOURNAL Physiology (Bethesda) 23:360-70 (2008) DOI:10.1152/physiol.00026.2008 REFERENCE PMID:17684094 AUTHORS Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andre E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P TITLE 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. JOURNAL Proc Natl Acad Sci U S A 104:13519-24 (2007) DOI:10.1073/pnas.0705923104 REFERENCE PMID:21841075 AUTHORS Latorre R, Brauchi S, Madrid R, Orio P TITLE A cool channel in cold transduction. JOURNAL Physiology (Bethesda) 26:273-85 (2011) DOI:10.1152/physiol.00004.2011 REFERENCE PMID:20932256 AUTHORS Babes A, Ciobanu AC, Neacsu C, Babes RM TITLE TRPM8, a sensor for mild cooling in mammalian sensory nerve endings. JOURNAL Curr Pharm Biotechnol 12:78-88 (2011) DOI:10.2174/138920111793937835 REFERENCE PMID:23000387 AUTHORS Loyd DR, Henry MA, Hargreaves KM TITLE Serotonergic neuromodulation of peripheral nociceptors. JOURNAL Semin Cell Dev Biol 24:51-7 (2013) DOI:10.1016/j.semcdb.2012.09.002 REFERENCE PMID:17124270 AUTHORS Grant AD, Cottrell GS, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle N, Geppetti P, Bunnett NW TITLE Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. JOURNAL J Physiol 578:715-33 (2007) DOI:10.1113/jphysiol.2006.121111 REFERENCE PMID:22470230 AUTHORS Mandadi S, Armati PJ, Roufogalis BD TITLE Protein kinase C modulation of thermo-sensitive transient receptor potential channels: Implications for pain signaling. JOURNAL J Nat Sci Biol Med 2:13-25 (2011) DOI:10.4103/0976-9668.82311 REL_PATHWAY map00590 Arachidonic acid metabolism map04010 MAPK signaling pathway map04020 Calcium signaling pathway KO_PATHWAY ko04750 /// ENTRY map07013 Drug Pathway NAME Cephalosporins - oral agents PATHWAY_MAP map07013 Cephalosporins - oral agents COMPOUND C00916 Cephalosporin C D00256 Cefaclor (JP18) D00257 Cefadroxil (JAN) D00258 Cefixime (INN) D00261 Cefprozil (USP) D00263 Cefalexin (JP18) D00264 Cephradine (USP) D00906 Cephalexin (USP) D00914 Cefuroxime axetil (JP18/USP/INN) D00916 Loracarbef (USP) D00917 Cefdinir (JP18/USP/INN) D00920 Cefpodoxime proxetil (JP18/USP) D00922 Ceftibuten (USAN/INN) D00923 Ceftizoxime sodium (JP18/USP) D01415 Cefotiam hexetil hydrochloride (JP18) D01628 Cefditoren pivoxil (JP18/USAN) D01629 Cefetamet pivoxil hydrochloride (JAN) D01680 Cefcapene pivoxil hydrochloride hydrate (JP18) D01686 Cefteram pivoxil (JP18) D01949 Cefaloglycin (JAN) D02121 Ceftibuten hydrate (JP18) D02352 Cefaclor (USP) D02353 Cefadroxil (USP) D03438 Cephalexin hydrochloride (USP) D07640 Cefixime (USP) D07651 Cefprozil (INN) D07658 Ceftizoxime (INN) D08143 Loracarbef (INN) REFERENCE AUTHORS Fukai S. TITLE [New Drugs Today (6th ed)] (In Japanese) JOURNAL Jiho (1995) REFERENCE AUTHORS Walter S. TITLE Drug Discovery: A History JOURNAL Wiley (2005) REFERENCE AUTHORS Bertram GK (ed). TITLE Basic & Clinical Pharmacology (9th ed) JOURNAL Lange (2004) REFERENCE AUTHORS Matsumoto K. TITLE [Cephem Antibiotics] (In Japanese) JOURNAL Iyaku journal (1991) REFERENCE PMID:3501757 AUTHORS Jones RN, Barry AL. TITLE Beta-lactamase hydrolysis and inhibition studies of the new 1-carbacephem LY163892. JOURNAL Eur J Clin Microbiol 6:570-1 (1987) DOI:10.1007/BF02014248 REL_PATHWAY map00311 Penicillin and cephalosporin biosynthesis map07012 Cephalosporins - parenteral agents /// ENTRY map07018 Drug Pathway NAME Sulfonamide derivatives - hypoglycemic agents PATHWAY_MAP map07018 Sulfonamide derivatives - hypoglycemic agents COMPOUND D00219 Acetohexamide (JP18/USP/INN) D00271 Chlorpropamide (JP18/USP/INN) D00335 Glipizide (USP/INN) D00336 Glyburide (USP) D00379 Tolazamide (JAN/USP/INN) D00380 Tolbutamide (JAN/USP/INN) D00593 Glimepiride (JP18/USP/INN) D01210 Glybuzole (JAN/INN) D01356 Glymidine sodium (JAN/USAN/INN) D01599 Gliclazide (JP18/INN) D01799 Glyclopyramide (JAN/INN) D02424 Glyprothiazol (INN) D02425 Carbutamide (INN) D02426 Glycyclamide (INN) D02427 Glibornuride (USAN/INN) D02431 Gliflumide (USAN) D02432 Glicetanile sodium (USAN) D02462 Glybuthiazol (INN) D08543 Sulfanilamide (INN) REFERENCE AUTHORS Sano T, Naito T, Kubo T (eds). TITLE [Medicinal Chemistry, an Introduction (7th ed)] (In Japanese) JOURNAL Nankodo (2002) REFERENCE AUTHORS Fukai S. TITLE [New Drugs Today (6th ed)] (In Japanese) JOURNAL Jiho (1995) REFERENCE AUTHORS Walter S. TITLE Drug Discovery: A History JOURNAL Wiley (2005) REFERENCE AUTHORS Japan Pharmaceutical Association (ed). TITLE [Face of Medecine: Structure Activity Relationship] (In Japanese) JOURNAL Yakuji Nippo (1999) /// ENTRY map07019 Drug Pathway NAME Tetracyclines PATHWAY_MAP map07019 Tetracyclines COMPOUND D00201 Tetracycline (JAN/USP/INN) D00205 Oxytetracycline (JAN/USP/INN) D00290 Demeclocycline hydrochloride (USP) D00307 Doxycycline (USP) D00849 Methacycline hydrochloride (JAN/USP) D00850 Minocycline hydrochloride (JP18/USP) D01079 Tigecycline (JAN/USP) D01596 Oxytetracycline hydrochloride (JP18/USP) D02122 Tetracycline hydrochloride (JP18/USP) D02129 Doxycycline hyclate (USP) D02255 Chlortetracycline hydrochloride (JAN/USP) D03477 Chlortetracycline bisulfate (USP) D03680 Demeclocycline (USP) D03903 Doxycycline calcium (USP) D04972 Methacycline (USAN) D05045 Minocycline (USAN/INN) D05322 Oxytetracycline calcium (USP) D07689 Chlortetracycline (INN) D07876 Doxycycline (INN) D07877 Doxycycline hydrochloride REFERENCE AUTHORS Fukai S. TITLE [New Drugs Today (6th ed)] (In Japanese) JOURNAL Jiho (1995) REFERENCE AUTHORS Walter S. TITLE Drug Discovery: A History JOURNAL Wiley (2005) REFERENCE AUTHORS Japan Pharmaceutical Association (ed). TITLE [Face of Medecine: Structure Activity Relationship] (In Japanese) JOURNAL Yakuji Nippo (1999) REFERENCE AUTHORS Zimmerman TJ, Kooner K, Sharir M, Fechtner RD (eds). TITLE Textbook of Ocular Pharmacology (1997) JOURNAL Lippincott Williams & Wilkins (1997) REFERENCE AUTHORS Hunter IS, Hill RA. TITLE Tetracyclines. JOURNAL Drugs and the Pharmaceutical Sciences 82:659-682 (1997) REFERENCE AUTHORS Nelson ML. TITLE The chemistry and biology of the tetracyclines. JOURNAL Annu Rep Med Chem 37:105-114 (2002) DOI:10.1007/978-3-0348-8306-1_1 REFERENCE PMID:2280462 AUTHORS Kobayashi Y. TITLE [Tetracyclines] JOURNAL Nippon Rinsho 48:2184-8 (1990) REFERENCE PMID:7628979 AUTHORS Tally FT, Ellestad GA, Testa RT. TITLE Glycylcyclines: a new generation of tetracyclines. JOURNAL J Antimicrob Chemother 35:449-52 (1995) DOI:10.1093/jac/35.4.449 REFERENCE PMID:12237079 AUTHORS Chopra I. TITLE New developments in tetracycline antibiotics: glycylcyclines and tetracycline efflux pump inhibitors. JOURNAL Drug Resist Updat 5:119-25 (2002) DOI:10.1016/S1368-7646(02)00051-1 REFERENCE PMID:16249141 AUTHORS Scheinfeld N. TITLE Tigecycline: a review of a new glycylcycline antibiotic. JOURNAL J Dermatolog Treat 16:207-12 (2005) DOI:10.1080/09546630510011810 REL_PATHWAY map00253 Tetracycline biosynthesis /// ENTRY map01230 Overview Pathway NAME Biosynthesis of amino acids DESCRIPTION This map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module for conversion of three-carbon compounds from glyceraldehyde-3P to pyruvate [MD:M00002], together with the pathways around serine and glycine. This KEGG module is the most conserved one in the KEGG MODULE database and is found in almost all the completely sequenced genomes. The extensions are the pathways containing the reaction modules RM001, RM033, RM032, and RM002 for biosynthesis of branched-chain amino acids (left) and basic amino acids (bottom), and the pathways for biosynthesis of histidine and aromatic amino acids (top right). It is interesting to note that the so-called essential amino acids that cannot be synthesized in human and other organisms generally appear in these extensions. Furthermore, the bottom extension of basic amino acids appears to be most divergent containing multiple pathways for lysine biosynthesis and multiple gene sets for arginine biosynthesis. PATHWAY_MAP map01230 Biosynthesis of amino acids MODULE M00002 Glycolysis, core module involving three-carbon compounds [PATH:map01230] M00005 PRPP biosynthesis, ribose-5P => PRPP [PATH:map01230] M00007 Pentose phosphate pathway, non-oxidative phase, fructose-6P => ribose-5P [PATH:map01230] M00010 Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate [PATH:map01230] M00015 Proline biosynthesis, glutamate => proline [PATH:map01230] M00016 Lysine biosynthesis, succinyl-DAP pathway, aspartate => lysine [PATH:map01230] M00017 Methionine biosynthesis, aspartate => homoserine => methionine [PATH:map01230] M00018 Threonine biosynthesis, aspartate => homoserine => threonine [PATH:map01230] M00019 Valine/isoleucine biosynthesis, pyruvate => valine / 2-oxobutanoate => isoleucine [PATH:map01230] M00020 Serine biosynthesis, glycerate-3P => serine [PATH:map01230] M00021 Cysteine biosynthesis, serine => cysteine [PATH:map01230] M00022 Shikimate pathway, phosphoenolpyruvate + erythrose-4P => chorismate [PATH:map01230] M00023 Tryptophan biosynthesis, chorismate => tryptophan [PATH:map01230] M00024 Phenylalanine biosynthesis, chorismate => phenylpyruvate => phenylalanine [PATH:map01230] M00025 Tyrosine biosynthesis, chorismate => HPP => tyrosine [PATH:map01230] M00026 Histidine biosynthesis, PRPP => histidine [PATH:map01230] M00028 Ornithine biosynthesis, glutamate => ornithine [PATH:map01230] M00029 Urea cycle [PATH:map01230] M00030 Lysine biosynthesis, AAA pathway, 2-oxoglutarate => 2-aminoadipate => lysine [PATH:map01230] M00031 Lysine biosynthesis, mediated by LysW, 2-aminoadipate => lysine [PATH:map01230] M00033 Ectoine biosynthesis, aspartate => ectoine [PATH:map01230] M00040 Tyrosine biosynthesis, chorismate => arogenate => tyrosine [PATH:map01230] M00338 Cysteine biosynthesis, homocysteine + serine => cysteine [PATH:map01230] M00345 Formaldehyde assimilation, ribulose monophosphate pathway [PATH:map01230] M00432 Leucine biosynthesis, 2-oxoisovalerate => 2-oxoisocaproate [PATH:map01230] M00433 Lysine biosynthesis, 2-oxoglutarate => 2-oxoadipate [PATH:map01230] M00525 Lysine biosynthesis, acetyl-DAP pathway, aspartate => lysine [PATH:map01230] M00526 Lysine biosynthesis, DAP dehydrogenase pathway, aspartate => lysine [PATH:map01230] M00527 Lysine biosynthesis, DAP aminotransferase pathway, aspartate => lysine [PATH:map01230] M00535 Isoleucine biosynthesis, pyruvate => 2-oxobutanoate [PATH:map01230] M00570 Isoleucine biosynthesis, threonine => 2-oxobutanoate => isoleucine [PATH:map01230] M00580 Pentose phosphate pathway, archaea, fructose-6P => ribose-5P [PATH:map01230] M00608 2-Oxocarboxylic acid chain extension, 2-oxoglutarate => 2-oxoadipate => 2-oxopimelate => 2-oxosuberate [PATH:map01230] M00609 Cysteine biosynthesis, methionine => cysteine [PATH:map01230] M00763 Ornithine biosynthesis, mediated by LysW, glutamate => ornithine [PATH:map01230] M00844 Arginine biosynthesis, ornithine => arginine [PATH:map01230] M00845 Arginine biosynthesis, glutamate => acetylcitrulline => arginine [PATH:map01230] M00910 Phenylalanine biosynthesis, chorismate => arogenate => phenylalanine [PATH:map01230] KO_PATHWAY ko01230 /// ENTRY map01059 Pathway NAME Biosynthesis of enediyne antibiotics DESCRIPTION Enediyne natural products are potent antitumor antibiotics produced by a variety of Actinomycetes. Enediyne has a unique structure consisting of three building blocks: aromatic, sugar and enediyne core. The enediyne core contains two acetylenic groups conjugated to a double bond in a 9- or 10-membered ring, and it is synthesized by an iterative type I polyketide synthase and other tailoring proteins [MD:M00824 M00825]. The 10-membered enediyne such as calicheamicin also contains an allylic trisulfide group, which acts as a trigger for diradical formation. This diagram shows the biosynthesis of C-1027, maduropeptin, neocarzinostatin, kedarcidin and calicheamicin. Some aromatic moieties are synthesized via iterative type I polyketide synthases, and others are derived from chorismate and aromatic amino acids such as tyrosine and azatyrosine [MD:M00829 M00830 M00831 M00834 M00826 M00827 M00828 M00832]. Finally, the aromatic and sugar building blocks are attached to the enediyne core by acyltransferases, condensation enzymes and glucosyltransferases [MD:M00833]. CLASS Metabolism; Metabolism of terpenoids and polyketides PATHWAY_MAP map01059 Biosynthesis of enediyne antibiotics MODULE M00824 9-membered enediyne core biosynthesis, malonyl-CoA => 3-hydroxyhexadeca-4,6,8,10,12,14-hexaenoyl-ACP => 9-membered enediyne core [PATH:map01059] M00825 10-membered enediyne core biosynthesis, malonyl-CoA => 3-hydroxyhexadeca-4,6,8,10,12,14-hexaenoyl-ACP => 10-membered enediyne core [PATH:map01059] M00826 C-1027 benzoxazolinate moiety biosynthesis, chorismate => benzoxazolinyl-CoA [PATH:map01059] M00827 C-1027 beta-amino acid moiety biosynthesis, tyrosine => 3-chloro-4,5-dihydroxy-beta-phenylalanyl-PCP [PATH:map01059] M00828 Maduropeptin beta-hydroxy acid moiety biosynthesis, tyrosine => 3-(4-hydroxyphenyl)-3-oxopropanoyl-PCP [PATH:map01059] M00829 3,6-Dimethylsalicylyl-CoA biosynthesis, malonyl-CoA => 6-methylsalicylate => 3,6-dimethylsalicylyl-CoA [PATH:map01059] M00830 Neocarzinostatin naphthoate moiety biosynthesis, malonyl-CoA => 2-hydroxy-5-methyl-1-naphthoate => 2-hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA [PATH:map01059] M00831 Kedarcidin 2-hydroxynaphthoate moiety biosynthesis, malonyl-CoA => 3,6,8-trihydroxy-2-naphthoate => 3-hydroxy-7,8-dimethoxy-6-isopropoxy-2-naphthoyl-CoA [PATH:map01059] M00832 Kedarcidin 2-aza-3-chloro-beta-tyrosine moiety biosynthesis, azatyrosine => 2-aza-3-chloro-beta-tyrosyl-PCP [PATH:map01059] M00833 Calicheamicin biosynthesis, calicheamicinone => calicheamicin [PATH:map01059] M00834 Calicheamicin orsellinate moiety biosynthesis, malonyl-CoA => orsellinate-ACP => 5-iodo-2,3-dimethoxyorsellinate-ACP [PATH:map01059] REFERENCE PMID:20336235 AUTHORS Liang ZX TITLE Complexity and simplicity in the biosynthesis of enediyne natural products. JOURNAL Nat Prod Rep 27:499-528 (2010) DOI:10.1039/b908165h REFERENCE PMID:18397168 AUTHORS Van Lanen SG, Shen B TITLE Biosynthesis of enediyne antitumor antibiotics. JOURNAL Curr Top Med Chem 8:448-59 (2008) DOI:10.2174/156802608783955656 REFERENCE PMID:12183628 AUTHORS Liu W, Christenson SD, Standage S, Shen B TITLE Biosynthesis of the enediyne antitumor antibiotic C-1027. JOURNAL Science 297:1170-3 (2002) DOI:10.1126/science.1072110 REFERENCE PMID:12183629 AUTHORS Ahlert J, Shepard E, Lomovskaya N, Zazopoulos E, Staffa A, Bachmann BO, Huang K, Fonstein L, Czisny A, Whitwam RE, Farnet CM, Thorson JS TITLE The calicheamicin gene cluster and its iterative type I enediyne PKS. JOURNAL Science 297:1173-6 (2002) DOI:10.1126/science.1072105 REFERENCE PMID:17918933 AUTHORS Van Lanen SG, Oh TJ, Liu W, Wendt-Pienkowski E, Shen B TITLE Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis. JOURNAL J Am Chem Soc 129:13082-94 (2007) DOI:10.1021/ja073275o REFERENCE PMID:15797213 AUTHORS Liu W, Nonaka K, Nie L, Zhang J, Christenson SD, Bae J, Van Lanen SG, Zazopoulos E, Farnet CM, Yang CF, Shen B TITLE The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. JOURNAL Chem Biol 12:293-302 (2005) DOI:10.1016/j.chembiol.2004.12.013 REFERENCE PMID:23360970 AUTHORS Lohman JR, Huang SX, Horsman GP, Dilfer PE, Huang T, Chen Y, Wendt-Pienkowski E, Shen B TITLE Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics. JOURNAL Mol Biosyst 9:478-91 (2013) DOI:10.1039/c3mb25523a REFERENCE PMID:19362637 AUTHORS Horsman GP, Van Lanen SG, Shen B TITLE Iterative type I polyketide synthases for enediyne core biosynthesis. JOURNAL Methods Enzymol 459:97-112 (2009) DOI:10.1016/S0076-6879(09)04605-9 REFERENCE PMID:20024241 AUTHORS Sun H, Kong R, Zhu D, Lu M, Ji Q, Liew CW, Lescar J, Zhong G, Liang ZX TITLE Products of the iterative polyketide synthases in 9- and 10-membered enediyne biosynthesis. JOURNAL Chem Commun (Camb) 7399-401 (2009) DOI:10.1039/b916751j REFERENCE PMID:18223152 AUTHORS Zhang J, Van Lanen SG, Ju J, Liu W, Dorrestein PC, Li W, Kelleher NL, Shen B TITLE A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. JOURNAL Proc Natl Acad Sci U S A 105:1460-5 (2008) DOI:10.1073/pnas.0711625105 REFERENCE PMID:19689130 AUTHORS Belecki K, Crawford JM, Townsend CA TITLE Production of octaketide polyenes by the calicheamicin polyketide synthase CalE8: implications for the biosynthesis of enediyne core structures. JOURNAL J Am Chem Soc 131:12564-6 (2009) DOI:10.1021/ja904391r REFERENCE PMID:19357082 AUTHORS Kotaka M, Kong R, Qureshi I, Ho QS, Sun H, Liew CW, Goh LP, Cheung P, Mu Y, Lescar J, Liang ZX TITLE Structure and catalytic mechanism of the thioesterase CalE7 in enediyne biosynthesis. JOURNAL J Biol Chem 284:15739-49 (2009) DOI:10.1074/jbc.M809669200 REFERENCE PMID:24041368 AUTHORS Belecki K, Townsend CA TITLE Biochemical determination of enzyme-bound metabolites: preferential accumulation of a programmed octaketide on the enediyne polyketide synthase CalE8. JOURNAL J Am Chem Soc 135:14339-48 (2013) DOI:10.1021/ja406697t REFERENCE PMID:20534556 AUTHORS Horsman GP, Chen Y, Thorson JS, Shen B TITLE Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes. JOURNAL Proc Natl Acad Sci U S A 107:11331-5 (2010) DOI:10.1073/pnas.1003442107 REFERENCE PMID:25278375 AUTHORS Chen X, Ji R, Jiang X, Yang R, Liu F, Xin Y TITLE Iterative type I polyketide synthases involved in enediyne natural product biosynthesis. JOURNAL IUBMB Life 66:587-95 (2014) DOI:10.1002/iub.1316 REFERENCE PMID:19856960 AUTHORS Lin S, Horsman GP, Chen Y, Li W, Shen B TITLE Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. JOURNAL J Am Chem Soc 131:16410-7 (2009) DOI:10.1021/ja901242s REFERENCE PMID:23844627 AUTHORS Horsman GP, Lechner A, Ohnishi Y, Moore BS, Shen B TITLE Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics. JOURNAL Biochemistry 52:5217-24 (2013) DOI:10.1021/bi400572a REFERENCE PMID:20704329 AUTHORS Lin S, Horsman GP, Shen B TITLE Characterization of the epoxide hydrolase NcsF2 from the neocarzinostatin biosynthetic gene cluster. JOURNAL Org Lett 12:3816-9 (2010) DOI:10.1021/ol101473t REFERENCE PMID:18182490 AUTHORS Van Lanen SG, Lin S, Shen B TITLE Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism. JOURNAL Proc Natl Acad Sci U S A 105:494-9 (2008) DOI:10.1073/pnas.0708750105 REFERENCE PMID:14580219 AUTHORS Christenson SD, Wu W, Spies MA, Shen B, Toney MD TITLE Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. JOURNAL Biochemistry 42:12708-18 (2003) DOI:10.1021/bi035223r REFERENCE PMID:16887797 AUTHORS Van Lanen SG, Lin S, Dorrestein PC, Kelleher NL, Shen B TITLE Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027. JOURNAL J Biol Chem 281:29633-40 (2006) DOI:10.1074/jbc.M605887200 REFERENCE PMID:16104723 AUTHORS Van Lanen SG, Dorrestein PC, Christenson SD, Liu W, Ju J, Kelleher NL, Shen B TITLE Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates. JOURNAL J Am Chem Soc 127:11594-5 (2005) DOI:10.1021/ja052871k REFERENCE PMID:18426211 AUTHORS Lin S, Van Lanen SG, Shen B TITLE Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. JOURNAL J Am Chem Soc 130:6616-23 (2008) DOI:10.1021/ja710601d REFERENCE PMID:19817865 AUTHORS Van Lanen SG, Lin S, Horsman GP, Shen B TITLE Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. JOURNAL FEMS Microbiol Lett 300:237-41 (2009) DOI:10.1111/j.1574-6968.2009.01802.x REFERENCE PMID:23034235 AUTHORS Lohman JR, Shen B TITLE 4-methylideneimidazole-5-one-containing aminomutases in enediyne biosynthesis. JOURNAL Methods Enzymol 516:299-319 (2012) DOI:10.1016/B978-0-12-394291-3.00007-1 REFERENCE PMID:20718468 AUTHORS Ling J, Horsman GP, Huang SX, Luo Y, Lin S, Shen B TITLE Enediyne antitumor antibiotic maduropeptin biosynthesis featuring a C-methyltransferase that acts on a CoA-tethered aromatic substrate. JOURNAL J Am Chem Soc 132:12534-6 (2010) DOI:10.1021/ja1050814 REFERENCE PMID:23633564 AUTHORS Huang SX, Lohman JR, Huang T, Shen B TITLE A new member of the 4-methylideneimidazole-5-one-containing aminomutase family from the enediyne kedarcidin biosynthetic pathway. JOURNAL Proc Natl Acad Sci U S A 110:8069-74 (2013) DOI:10.1073/pnas.1304733110 REFERENCE PMID:18561189 AUTHORS McCoy JG, Johnson HD, Singh S, Bingman CA, Lei IK, Thorson JS, Phillips GN Jr TITLE Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway. JOURNAL Proteins 74:50-60 (2009) DOI:10.1002/prot.22131 REFERENCE PMID:24978950 AUTHORS Singh S, Nandurkar NS, Thorson JS TITLE Characterization of the calicheamicin orsellinate C2-O-methyltransferase CalO6. 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JOURNAL J Biol Chem 276:18765-74 (2001) DOI:10.1074/jbc.M101225200 REL_PATHWAY map00253 Tetracycline biosynthesis map01056 Biosynthesis of type II polyketide backbone KO_PATHWAY ko01057 /// ENTRY C00099 Compound NAME beta-Alanine; 3-Aminopropionic acid; 3-Aminopropanoate FORMULA C3H7NO2 EXACT_MASS 89.0477 MOL_WEIGHT 89.09 REMARK Same as: D07561 REACTION R00489 R00904 R00905 R00906 R00907 R00908 R00909 R00910 R00911 R00912 R00913 R00914 R00915 R00916 R00917 R01164 R01166 R02473 R02474 R02741 R03286 R03288 R03935 R09379 R09648 R10821 PATHWAY map00240 Pyrimidine metabolism map00410 beta-Alanine metabolism map00640 Propanoate metabolism map00770 Pantothenate and CoA biosynthesis map01100 Metabolic pathways map01110 Biosynthesis of secondary metabolites map01240 Biosynthesis of cofactors map04080 Neuroactive ligand-receptor interaction map04974 Protein digestion and absorption MODULE M00046 Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate M00119 Pantothenate biosynthesis, valine/L-aspartate => pantothenate M00913 Pantothenate biosynthesis, 2-oxoisovalerate/spermine => pantothenate ENZYME 1.2.1.3 1.2.1.5 1.2.1.19 1.5.1.26 2.6.1.18 2.6.1.19 2.6.1.55 2.6.1.120 2.8.3.- 3.4.13.4 3.4.13.5 3.4.13.18 3.4.13.20 3.5.1.6 3.5.1.21 3.5.1.22 3.5.1.100 3.5.3.17 4.1.1.11 4.1.1.15 6.3.2.1 6.3.2.11 6.3.2.23 6.3.2.36 6.3.2.44 BRITE Compounds with biological roles [BR:br08001] Peptides Amino acids Other amino acids C00099 beta-Alanine Amines Biogenic amines C00099 beta-Alanine DBLINKS CAS: 107-95-9 PubChem: 3399 KNApSAcK: C00001333 PDB-CCD: BAL NIKKAJI: J4.070C ATOM 6 1 C1b C 25.6778 -16.8919 2 C6a C 24.4732 -16.1936 3 C1b C 26.8940 -16.1936 4 O6a O 23.2571 -16.8978 5 O6a O 24.4732 -14.7912 6 N1a N 28.1045 -16.8919 BOND 5 1 1 2 1 2 1 3 1 3 2 4 1 4 2 5 2 5 3 6 1 ///