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
Biosynthesis of 12-, 14- and 16-membered macrolides
Biosynthesis of secondary metabolites
Orthology
K10817  
erythronolide synthase
Genes
SEN: 
SACE_0721(eryAI) SACE_0723(eryAII) SACE_0724(eryAIII)
Taxonomy
Reference
1
  Authors
Omura, S. and Nakagawa, A.
  Title
Biosynthesis of 16-membered macrolide antibiotics.
  Journal
Antibiotics 4 (1981) 175-192.
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 (1984) 642-643.
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 (2001) 1790-2.
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 (2001) 14808-13.
  Sequence
[up:Q03133]
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 (2007) 195-221.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
87683-77-0

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