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
Biosynthesis of 12-, 14- and 16-membered macrolides
ko00522

All organismsOrtholog table
Orthology
K15988  
tylactone synthase
K15989  
tylactone mycaminosyltransferase [EC:2.4.1.316]
K15990  
mycaminosyltransferase auxiliary protein tylMIII
K15991  
20-oxo-5-O-mycaminosyltylactone 23-monooxygenase [EC:1.14.13.186]
K15992  
cytochrome P450 TylI
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  
erythronolide synthase [EC:2.3.1.94]
K14366  
6-deoxyerythronolide B hydroxylase [EC:1.14.13.188]
K14367  
erythronolide B dTDP-mycarose O-glycosyltransferase [EC2.4.1.-]
K14368  
L-desosaminyltransferase [EC:2.4.1.278]
K15997  
desosaminyltransferase auxiliary protein
K14369  
erythromycin 3''-O-methyltransferase [EC:2.1.1.254]
K14370  
erythromycin 12 hydroxylase [EC:1.14.13.154]
K15998  
TDP-megosamine glycosyltransferase
K15999  
mycarose O-acyltransferase
K16000  
type I polyketide synthase PikAI
K16001  
type I polyketide synthase PikAII
K16002  
type I polyketide synthase PikAIII
K16003  
type I polyketide synthase PikAIV
K16004  
glycosyltransferase DesVII [EC:2.4.1.277]
K16005  
glycosyltransferase auxiliary protein DesVIII
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)
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)
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)
Reference
  Authors
Katz L
  Title
The DEBS paradigm for type I modular polyketide synthases and beyond.
  Journal
Methods Enzymol 459:113-42 (2009)
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)
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)
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)
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)
Reference
  Authors
Ikeda H, Omura S
  Title
Avermectin Biosynthesis.
  Journal
Chem Rev 97:2591-2610 (1997)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Reference
  Authors
Rawlings BJ.
  Title
Type I polyketide biosynthesis in bacteria (part B).
  Journal
Nat Prod Rep 18:231-81 (2001)
Reference
  Authors
Rawlings BJ.
  Title
Type I polyketide biosynthesis in bacteria (Part A--erythromycin biosynthesis).
  Journal
Nat Prod Rep 18:190-227 (2001)
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)
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)
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)
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)
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)
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)
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)

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