KEGG   PATHWAY: ko00522Help
Entry
ko00522                     Pathway                                

Name
Biosynthesis of 12-, 14- and 16-membered macrolides
Class
Metabolism; Metabolism of terpenoids and polyketides
BRITE hierarchy
Pathway map
ko00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ko00522

Ortholog table
Module
M00773  Tylosin biosynthesis, methylmalonyl-CoA + malonyl-CoA => tylactone => tylosin [PATH:ko00522]
M00774  Erythromycin biosynthesis, propanoyl-CoA + methylmalonyl-CoA => deoxyerythronolide B => erythromycin A/B [PATH:ko00522]
M00775  Oleandomycin biosynthesis, malonyl-CoA + methylmalonyl-CoA => 8,8a-deoxyoleandolide => oleandomycin [PATH:ko00522]
M00776  Pikromycin/methymycin/neomethymycin biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin/neomethymycin [PATH:ko00522]
M00777  Avermectin biosynthesis, 2-methylbutanoyl-CoA/isobutyryl-CoA => 6,8a-Seco-6,8a-deoxy-5-oxoavermectin 1a/1b aglycone => avermectin A1a/B1a/A1b/B1b [PATH:ko00522]
Orthology
K15988  tylactone synthase
K15989  tylactone mycaminosyltransferase [EC:2.4.1.316]
K15990  tylactone mycaminosyltransferase auxiliary protein
K15992  cytochrome P450 TylI
K15991  20-oxo-5-O-mycaminosyltylactone 23-monooxygenase [EC:1.14.13.186]
K15993  O-mycaminosyltylonolide 6-deoxyallosyltransferase [EC:2.4.1.317]
K15994  demethyllactenocin mycarosyltransferase [EC:2.4.1.318]
K15995  demethylmacrocin O-methyltransferase [EC:2.1.1.102]
K15996  macrocin O-methyltransferase [EC:2.1.1.101]
K10817  6-deoxyerythronolide-B synthase [EC:2.3.1.94]
K14366  6-deoxyerythronolide B hydroxylase [EC:1.14.13.188]
K14367  erythronolide mycarosyltransferase [EC:2.4.1.328]
K14368  3-alpha-mycarosylerythronolide B desosaminyl transferase [EC:2.4.1.278]
K15997  3-alpha-mycarosylerythronolide B desosaminyl transferase auxiliary protein
K14370  erythromycin 12 hydroxylase [EC:1.14.13.154]
K14369  erythromycin 3''-O-methyltransferase [EC:2.1.1.254]
K15998  TDP-megosamine glycosyltransferase
K19698  TDP-megosamine glycosyltransferase auxiliary protein
K15999  mycarose O-acyltransferase
K16000  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.239 2.3.1.240]
K16001  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.239 2.3.1.240]
K16002  narbonolide/10-deoxymethynolide synthase [EC:2.3.1.239 2.3.1.240]
K16003  narbonolide synthase [EC:2.3.1.240]
K16004  narbonolide/10-deoxymethynolide desosaminyltransferase [EC:2.4.1.277]
K16005  narbonolide/10-deoxymethynolide desosaminyltransferase auxiliary protein
K16006  pikromycin synthase [EC:1.14.13.185]
K16007  8,8a-deoxyoleandolide synthase
K16008  cytochrome P450 monooxygenase OleP
K16009  glycosyltransferase OleGII
K13320  L-olivosyl-oleandolide 3-O-methyltransferase [EC:2.1.1.239]
K16010  desosaminyltransferase OleGI
K14371  type I polyketide synthase AVES
K14372  cytochrome P450 hydroxylase [EC:1.14.-.-]
K14373  C-5 ketoreductase
K14374  avermectin B 5-O-methyltransferase [EC:2.1.1.-]
K14375  dTDP-L-oleandrosyltransferase [EC:2.4.1.-]
Compound
C00083  Malonyl-CoA
C00100  Propanoyl-CoA
C00630  2-Methylpropanoyl-CoA
C00683  (S)-Methylmalonyl-CoA
C00744  Macrocin
C01033  2-Methylbutanoyl-CoA
C01457  Tylosin
C01912  Erythromycin
C01946  Oleandomycin
C02400  Demethylmacrocin
C02557  Methylmalonyl-CoA
C03240  6-Deoxyerythronolide B
C06616  Erythromycin C
C06630  3-O-alpha-Mycarosylerythronolide B
C06633  Erythromycin D
C06634  Erythromycin E
C06635  Erythronolide B
C06653  Erythromycin B
C11911  dTDP-D-desosamine
C11912  dTDP-6-deoxy-D-allose
C11916  dTDP-L-mycarose
C11920  dTDP-L-olivose
C11921  dTDP-L-oleandrose
C11933  dTDP-D-mycaminose
C11953  6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''2b'' aglycone
C11954  5-Oxoavermectin ''2b'' aglycone
C11955  Avermectin B2b aglycone
C11956  Avermectin A2b aglycone
C11957  Avermectin B2b monosaccharide
C11958  Avermectin A2b monosaccharide
C11959  Avermectin B2b
C11960  Avermectin A2b
C11961  6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''1b'' aglycone
C11962  5-Oxoavermectin ''1b'' aglycone
C11963  Avermectin B1b aglycone
C11964  Avermectin A1b aglycone
C11965  Avermectin B1b monosaccharide
C11966  Avermectin A1b monosaccharide
C11967  Avermectin B1b
C11968  Avermectin A1b
C11969  6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''2a'' aglycone
C11970  5-Oxoavermectin ''2a'' aglycone
C11971  Avermectin B2a aglycone
C11972  Avermectin A2a aglycone
C11973  Avermectin B2a monosaccharide
C11974  Avermectin A2a monosaccharide
C11975  Avermectin B2a
C11976  Avermectin A2a
C11977  6,8a-Seco-6,8a-deoxy-5-oxoavermectin ''1a'' aglycone
C11978  5-Oxoavermectin ''1a'' aglycone
C11979  Avermectin B1a aglycone
C11980  Avermectin A1a aglycone
C11981  Avermectin B1a monosaccharide
C11982  Avermectin A1a monosaccharide
C11983  Avermectin B1a
C11984  Avermectin A1a
C11985  Megalomicin A
C11986  Megalomicin B
C11987  Megalomicin C1
C11988  Megalomicin C2
C11989  8,8a-Deoxyoleandolide
C11990  Oleandolide
C11991  L-Olivosyl-oleandolide
C11992  L-Oleandrosyl-oleandolide
C11993  10-Deoxymethynolide
C11994  10-Deoxymethymycin
C11995  Neomethymycin
C11996  Methymycin
C11997  Narbonolide
C11998  Narbomycin
C11999  Pikromycin
C12000  Tylactone
C12001  5-O-beta-D-Mycaminosyltylactone
C12002  5-O-beta-D-Mycaminosyltylonolide
C12003  Demethyllactenocin
C20760  20-Oxo-5-O-beta-mycaminosyltylactone
Reference
  Authors
Hertweck C
  Title
The biosynthetic logic of polyketide diversity.
  Journal
Angew Chem Int Ed Engl 48:4688-716 (2009)
DOI:10.1002/anie.200806121
Reference
  Authors
Long PF, Wilkinson CJ, Bisang CP, Cortes J, Dunster N, Oliynyk M, McCormick E, McArthur H, Mendez C, Salas JA, Staunton J, Leadlay PF
  Title
Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase.
  Journal
Mol Microbiol 43:1215-25 (2002)
DOI:10.1046/j.1365-2958.2002.02815.x
Reference
  Authors
Bisang C, Long PF, Cortes J, Westcott J, Crosby J, Matharu AL, Cox RJ, Simpson TJ, Staunton J, Leadlay PF
  Title
A chain initiation factor common to both modular and aromatic polyketide synthases.
  Journal
Nature 401:502-5 (1999)
DOI:10.1038/46829
Reference
  Authors
Katz L
  Title
The DEBS paradigm for type I modular polyketide synthases and beyond.
  Journal
Methods Enzymol 459:113-42 (2009)
DOI:10.1016/S0076-6879(09)04606-0
Reference
  Authors
Kittendorf JD, Beck BJ, Buchholz TJ, Seufert W, Sherman DH
  Title
Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase.
  Journal
Chem Biol 14:944-54 (2007)
DOI:10.1016/j.chembiol.2007.07.013
Reference
  Authors
Beck BJ, Yoon YJ, Reynolds KA, Sherman DH
  Title
The hidden steps of domain skipping: macrolactone ring size determination in the pikromycin modular polyketide synthase.
  Journal
Chem Biol 9:575-83 (2002)
DOI:10.1016/S1074-5521(02)00146-1
Reference
  Authors
Chen S, Roberts JB, Xue Y, Sherman DH, Reynolds KA
  Title
The Streptomyces venezuelae pikAV gene contains a transcription unit essential for expression of enzymes involved in glycosylation of narbonolide and 10-deoxymethynolide.
  Journal
Gene 263:255-64 (2001)
DOI:10.1016/S0378-1119(00)00560-6
Reference
  Authors
Kim BS, Cropp TA, Beck BJ, Sherman DH, Reynolds KA
  Title
Biochemical evidence for an editing role of thioesterase II in the biosynthesis of the polyketide pikromycin.
  Journal
J Biol Chem 277:48028-34 (2002)
DOI:10.1074/jbc.M207770200
Reference
  Authors
Ikeda H, Omura S
  Title
Avermectin Biosynthesis.
  Journal
Chem Rev 97:2591-2610 (1997)
DOI:10.1021/cr960023p
Reference
  Authors
Ikeda H, Nonomiya T, Omura S
  Title
Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases.
  Journal
J Ind Microbiol Biotechnol 27:170-6 (2001)
DOI:10.1038/sj.jim.7000092
Reference
  Authors
Volchegursky Y, Hu Z, Katz L, McDaniel R
  Title
Biosynthesis of the anti-parasitic agent megalomicin: transformation of erythromycin to megalomicin in Saccharopolyspora erythraea.
  Journal
Mol Microbiol 37:752-62 (2000)
DOI:10.1046/j.1365-2958.2000.02059.x
Reference
  Authors
Peiru S, Menzella HG, Rodriguez E, Carney J, Gramajo H
  Title
Production of the potent antibacterial polyketide erythromycin C in Escherichia coli.
  Journal
Appl Environ Microbiol 71:2539-47 (2005)
DOI:10.1128/AEM.71.5.2539-2547.2005
Reference
  Authors
Useglio M, Peiru S, Rodriguez E, Labadie GR, Carney JR, Gramajo H
  Title
TDP-L-megosamine biosynthesis pathway elucidation and megalomicin a production in Escherichia coli.
  Journal
Appl Environ Microbiol 76:3869-77 (2010)
DOI:10.1128/AEM.03083-09
Reference
  Authors
Tsai SC, Miercke LJ, Krucinski J, Gokhale R, Chen JC, Foster PG, Cane DE, Khosla C, Stroud RM
  Title
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel.
  Journal
Proc Natl Acad Sci U S A 98:14808-13 (2001)
DOI:10.1073/pnas.011399198
Reference
  Authors
Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B
  Title
Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate.
  Journal
J Biol Chem 284:29170-9 (2009)
DOI:10.1074/jbc.M109.003590
Reference
PMID:8300527
  Authors
Hsieh YJ, Kolattukudy PE.
  Title
Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea.
  Journal
J Bacteriol 176:714-24 (1994)
DOI:10.1128/JB.176.3.714-724.1994
Reference
PMID:8830278
  Authors
Donadio S, Staver MJ, Katz L.
  Title
Erythromycin production in Saccharopolyspora erythraea does not require a functional propionyl-CoA carboxylase.
  Journal
Mol Microbiol 19:977-84 (1996)
DOI:10.1046/j.1365-2958.1996.439969.x
Reference
PMID:9353926
  Authors
Summers RG, Donadio S, Staver MJ, Wendt-Pienkowski E, Hutchinson CR, Katz L.
  Title
Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production.
  Journal
Microbiology 143:3251-62 (1997)
DOI:10.1099/00221287-143-10-3251
Reference
  Authors
Rawlings BJ.
  Title
Type I polyketide biosynthesis in bacteria (part B).
  Journal
Nat Prod Rep 18:231-81 (2001)
DOI:10.1039/B100191O
Reference
  Authors
Rawlings BJ.
  Title
Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis).
  Journal
Nat Prod Rep 18:190-227 (2001)
DOI:10.1039/b009329g
Reference
  Authors
Borisova SA, Liu HW
  Title
Characterization of glycosyltransferase DesVII and its auxiliary partner protein DesVIII in the methymycin/picromycin biosynthetic pathway.
  Journal
Biochemistry 49:8071-84 (2010)
DOI:10.1021/bi1007657
Reference
  Authors
Hong JS, Park SJ, Parajuli N, Park SR, Koh HS, Jung WS, Choi CY, Yoon YJ
  Title
Functional analysis of desVIII homologues involved in glycosylation of macrolide antibiotics by interspecies complementation.
  Journal
Gene 386:123-30 (2007)
DOI:10.1016/j.gene.2006.08.021
Reference
  Authors
Rodriguez E, Peiru S, Carney JR, Gramajo H
  Title
In vivo characterization of the dTDP-D-desosamine pathway of the megalomicin gene cluster from Micromonospora megalomicea.
  Journal
Microbiology 152:667-73 (2006)
DOI:10.1099/mic.0.28680-0
Reference
  Authors
Moncrieffe MC, Fernandez MJ, Spiteller D, Matsumura H, Gay NJ, Luisi BF, Leadlay PF
  Title
Structure of the glycosyltransferase EryCIII in complex with its activating P450 homologue EryCII.
  Journal
J Mol Biol 415:92-101 (2012)
DOI:10.1016/j.jmb.2011.10.036
Reference
  Authors
Yuan Y, Chung HS, Leimkuhler C, Walsh CT, Kahne D, Walker S
  Title
In vitro reconstitution of EryCIII activity for the preparation of unnatural macrolides.
  Journal
J Am Chem Soc 127:14128-9 (2005)
DOI:10.1021/ja053704n
Reference
  Authors
Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM
  Title
The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 281:26289-97 (2006)
DOI:10.1074/jbc.M605478200
Reference
  Authors
Li S, Ouellet H, Sherman DH, Podust LM
  Title
Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae.
  Journal
J Biol Chem 284:5723-30 (2009)
DOI:10.1074/jbc.M807592200

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