KEGG   ORTHOLOGY: K10817Help
Entry
K10817                      KO                                     

Name
eryA
Definition
6-deoxyerythronolide-B synthase [EC:2.3.1.94]
Pathway
ko00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ko01052  Type I polyketide structures
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00774  Erythromycin biosynthesis, propanoyl-CoA + methylmalonyl-CoA => deoxyerythronolide B => erythromycin A/B
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01052 Type I polyketide structures
    K10817  eryA; 6-deoxyerythronolide-B synthase
   00522 Biosynthesis of 12-, 14- and 16-membered macrolides
    K10817  eryA; 6-deoxyerythronolide-B synthase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01004 Lipid biosynthesis proteins
    K10817  eryA; 6-deoxyerythronolide-B synthase
   01008 Polyketide biosynthesis proteins
    K10817  eryA; 6-deoxyerythronolide-B synthase
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.94  6-deoxyerythronolide-B synthase
     K10817  eryA; 6-deoxyerythronolide-B synthase
Lipid biosynthesis proteins [BR:ko01004]
 Polyketide synthase
  Modular PKS
   K10817  eryA; 6-deoxyerythronolide-B synthase
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide synthase (PKS)
  Modular type I PKS
   cis-AT PKS
    Erythronolide synthase
     K10817  eryA; 6-deoxyerythronolide-B synthase
BRITE hierarchy
Other DBs
RN: R00918
GO: 0047879
Genes
SEN: SACE_0721(eryAI) SACE_0723(eryAII) SACE_0724(eryAIII)
AEY: CDG81_13170
AG: AAG13917(megAI) AAG13918(megAII) AAG13919(megAIII)
TaxonomyKoalaUniProt
Reference
PMID:1618327
  Authors
Caffrey P, Bevitt DJ, Staunton J, Leadlay PF
  Title
Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea.
  Journal
FEBS Lett 304:225-8 (1992)
DOI:10.1016/0014-5793(92)80624-P

KEGG   ENZYME: 2.3.1.94Help
Entry
EC 2.3.1.94                 Enzyme                                 

Name
6-deoxyerythronolide-B synthase;
erythronolide condensing enzyme;
malonyl-CoA:propionyl-CoA malonyltransferase (cyclizing);
erythronolide synthase;
malonyl-CoA:propanoyl-CoA malonyltransferase (cyclizing);
deoxyerythronolide B synthase;
6-deoxyerythronolide B synthase;
DEBS
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
BRITE hierarchy
Sysname
propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing)
Reaction(IUBMB)
propanoyl-CoA + 6 (2S)-methylmalonyl-CoA + 6 NADPH + 6 H+ = 6-deoxyerythronolide B + 7 CoA + 6 CO2 + H2O + 6 NADP+ [RN:R00918]
Reaction(KEGG)
Substrate
propanoyl-CoA [CPD:C00100];
(2S)-methylmalonyl-CoA [CPD:C00683];
NADPH [CPD:C00005];
H+ [CPD:C00080]
Product
6-deoxyerythronolide B [CPD:C03240];
CoA [CPD:C00010];
CO2 [CPD:C00011];
H2O [CPD:C00001];
NADP+ [CPD:C00006]
Comment
The product, 6-deoxyerythronolide B, contains a 14-membered lactone ring and is an intermediate in the biosynthesis of erythromycin antibiotics. Biosynthesis of 6-deoxyerythronolide B requires 28 active sites that are precisely arranged along three large polypeptides, denoted DEBS1, -2 and -3 [6]. The polyketide product is synthesized by the processive action of a loading didomain, six extension modules and a terminal thioesterase domain [5]. Each extension module contains a minimum of a ketosynthase (KS), an acyltransferase (AT) and an acyl-carrier protein (ACP). The KS domain both accepts the growing polyketide chain from the previous module and catalyses the subsequent decarboxylative condensation between this substrate and an ACP-bound methylmalonyl extender unit, introduce by the AT domain. This combined effort gives rise to a new polyketide intermediate that has been extended by two carbon atoms [5].
History
EC 2.3.1.94 created 1989, modified 2008
Pathway
ec00522  Biosynthesis of 12-, 14- and 16-membered macrolides
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K10817  6-deoxyerythronolide-B synthase
Genes
SEN: SACE_0721(eryAI) SACE_0723(eryAII) SACE_0724(eryAIII)
AEY: CDG81_13170
Taxonomy
Reference
1
  Authors
Omura, S. and Nakagawa, A.
  Title
Biosynthesis of 16-membered macrolide antibiotics.
  Journal
Antibiotics 4:175-192 (1981)
Reference
2
  Authors
Roberts, G. and Leadley, P.F.
  Title
Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus.
  Journal
Biochem Soc Trans 12:642-643 (1984)
Reference
3  [PMID:11230695]
  Authors
Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE, Khosla C
  Title
Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli.
  Journal
Science 291:1790-2 (2001)
DOI:10.1126/science.1058092
Reference
4  [PMID:11752428]
  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
5  [PMID:17328673]
  Authors
Khosla C, Tang Y, Chen AY, Schnarr NA, Cane DE
  Title
Structure and mechanism of the 6-deoxyerythronolide B synthase.
  Journal
Annu Rev Biochem 76:195-221 (2007)
DOI:10.1146/annurev.biochem.76.053105.093515
Other DBs
ExplorEnz - The Enzyme Database: 2.3.1.94
IUBMB Enzyme Nomenclature: 2.3.1.94
ExPASy - ENZYME nomenclature database: 2.3.1.94
BRENDA, the Enzyme Database: 2.3.1.94
CAS: 87683-77-0

KEGG   REACTION: R00918Help
Entry
R00918                      Reaction                               

Name
propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing);
propanoyl-CoA:(2S)-methylmalonyl-CoA 2-C-acyltransferase (decarboxylating, oxoacyl-reducing and cyclizing)
Definition
Propanoyl-CoA + 6 (S)-Methylmalonyl-CoA + 6 NADPH + 6 H+ <=> 6-Deoxyerythronolide B + 7 CoA + 6 CO2 + H2O + 6 NADP+
Equation
C00100 + 6 C00683 + 6 C00005 + 6 C00080 <=> C03240 + 7 C00010 + 6 C00011 + C00001 + 6 C00006
Comment
EryA MegA
multi-step reaction
Reaction class
RC00001  C00005_C00006
RC00004  C00010_C00100  C00010_C00683
RC02825  C00100_C03240
RC02826  C00683_C03240
RC02828  C00683_C03240
RC02829  C00683_C03240
RC02830  C00683_C03240
RC02831  C00683_C03240
Enzyme
Pathway
rn00522  Biosynthesis of 12-, 14- and 16-membered macrolides
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00774  Erythromycin biosynthesis, propanoyl-CoA + methylmalonyl-CoA => deoxyerythronolide B => erythromycin A/B
Orthology
K10817  6-deoxyerythronolide-B synthase [EC:2.3.1.94]
Reference
1  [PMID:11752428]
  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
Other DBs
RHEA: 23071

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