Entry
Name
Biosynthesis of 12-, 14- and 16-membered macrolides
Including
Tylosin biosynthesis, Mycinamicin biosynthesis, Erythromycin biosynthesis, Oleandomycin biosynthesis, Pikromycin/methymycin biosynthesis, Avermectin biosynthesis
Class
Metabolism; Metabolism of terpenoids and polyketides
BRITE hierarchy
Pathway map
ko00522 Biosynthesis of 12-, 14- and 16-membered macrolides
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 biosynthesis, methylmalonyl-CoA + malonyl-CoA => narbonolide/10-deoxymethynolide => pikromycin/methymycin [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 ]
M00934 Mycinamicin biosynthesis, malonyl-CoA + methylmalonyl-CoA => protomycinolide IV => mycinamicin II [PATH:ko00522 ]
Orthology
K15990 tylactone mycaminosyltransferase auxiliary protein
K24528 protomycinolide IV synthase 1
K24559 protomycinolide IV synthase 2
K24560 protomycinolide IV synthase 3
K24561 protomycinolide IV synthase 4
K24562 protomycinolide IV synthase 5
K24529 protomycinolide IV desosaminyltransferase [EC:2.4.1.-]
K24292 mycinamicin VIII C21 methyl hydroxylase [EC:1.14.-.-]
K24531 mycinamicin VII 6-deoxyallosyltransferase [EC:2.4.1.-]
K24390 mycinamicin IV hydroxylase/epoxidase [EC:1.14.-.-]
K14368 3-alpha-mycarosylerythronolide B desosaminyl transferase [EC:2.4.1.278 ]
K15997 3-alpha-mycarosylerythronolide B desosaminyl transferase auxiliary protein
K15998 TDP-megosamine glycosyltransferase
K19698 TDP-megosamine glycosyltransferase auxiliary protein
K15999 mycarose O-acyltransferase
K16004 narbonolide/10-deoxymethynolide desosaminyltransferase [EC:2.4.1.277 ]
K16005 narbonolide/10-deoxymethynolide desosaminyltransferase auxiliary protein
K16007 8,8a-deoxyoleandolide synthase 1
K24565 8,8a-deoxyoleandolide synthase 2
K24566 8,8a-deoxyoleandolide synthase 3
K16008 cytochrome P450 monooxygenase OleP
K16009 glycosyltransferase OleGII
K16010 desosaminyltransferase OleGI
K14371 avermectin polyketide synthase AveA1
K24567 avermectin polyketide synthase AveA2
K24568 avermectin polyketide synthase AveA3
K24569 avermectin polyketide synthase AveA4
K14372 cytochrome P450 hydroxylase [EC:1.14.-.-]
K14374 avermectin B 5-O-methyltransferase [EC:2.1.1.-]
K14375 dTDP-L-oleandrosyltransferase [EC:2.4.1.-]
Compound
C06630 3-O-alpha-Mycarosylerythronolide B
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
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
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
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
C11992 L-Oleandrosyl-oleandolide
C12001 5-O-beta-D-Mycaminosyltylactone
C12002 5-O-beta-D-Mycaminosyltylonolide
C20760 20-Oxo-5-O-beta-mycaminosyltylactone
Reference
Authors
Hertweck C
Title
The biosynthetic logic of polyketide diversity.
Journal
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
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
Reference
Authors
Katz L
Title
The DEBS paradigm for type I modular polyketide synthases and beyond.
Journal
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
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
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
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
Reference
Authors
Ikeda H, Omura S
Title
Avermectin Biosynthesis.
Journal
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
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
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
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
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
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
Reference
Authors
Hsieh YJ, Kolattukudy PE.
Title
Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea.
Journal
Reference
Authors
Donadio S, Staver MJ, Katz L.
Title
Erythromycin production in Saccharopolyspora erythraea does not require a functional propionyl-CoA carboxylase.
Journal
Reference
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
Reference
Authors
Rawlings BJ.
Title
Type I polyketide biosynthesis in bacteria (part B).
Journal
Reference
Authors
Rawlings BJ.
Title
Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis).
Journal
Reference
Authors
Borisova SA, Liu HW
Title
Characterization of glycosyltransferase DesVII and its auxiliary partner protein DesVIII in the methymycin/picromycin biosynthetic pathway.
Journal
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
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
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
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
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
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
Related pathway
ko00280 Valine, leucine and isoleucine degradation
ko00523 Polyketide sugar unit biosynthesis
LinkDB
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