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

Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups

propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing)

propanoyl-CoA + 6 (2S)-methylmalonyl-CoA + 6 NADPH + 6 H+ = 6-deoxyerythronolide B + 7 CoA + 6 CO2 + H2O + 6 NADP+ [RN:R00918]

R00918

propanoyl-CoA [CPD:C00100];
(2S)-methylmalonyl-CoA [CPD:C00683];
NADPH [CPD:C00005];
H+ [CPD:C00080]

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].

1

Omura, S. and Nakagawa, A.

Biosynthesis of 16-membered macrolide antibiotics.

Antibiotics 4 (1981) 175-192.

2

Roberts, G. and Leadley, P.F.

Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus.

Biochem. Soc. Trans. 12 (1984) 642-643.

3  [PMID:11230695]

Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE, Khosla C

Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli.

Science. 291 (2001) 1790-2.

Saccharopolyspora erythraea [GN:sen]

4  [PMID:11752428]

Tsai SC, Miercke LJ, Krucinski J, Gokhale R, Chen JC, Foster PG, Cane DE, Khosla C, Stroud RM

Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel.

Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 14808-13.

5  [PMID:17328673]

Khosla C, Tang Y, Chen AY, Schnarr NA, Cane DE

Structure and mechanism of the 6-deoxyerythronolide B synthase.

Annu. Rev. Biochem. 76 (2007) 195-221.