The Enzyme Database

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Accepted name: 6-deoxyerythronolide-B synthase
Reaction: propanoyl-CoA + 6 (2S)-methylmalonyl-CoA + 6 NADPH + 6 H+ = 6-deoxyerythronolide B + 7 CoA + 6 CO2 + H2O + 6 NADP+
For diagram of reaction, click here
Other name(s): 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
Systematic name: propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing)
Comments: 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].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 87683-77-0
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.  Pfeifer, B.A., Admiraal, S.J., Gramajo, H., Cane, D.E. and Khosla, C. Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli. Science 291 (2001) 1790–1792. [DOI] [PMID: 11230695]
4.  Tsai, S.C., Miercke, L.J., Krucinski, J., Gokhale, R., Chen, J.C., Foster, P.G., Cane, D.E., Khosla, C. and Stroud, R.M. Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. Proc. Natl. Acad. Sci. USA 98 (2001) 14808–14813. [DOI] [PMID: 11752428]
5.  Khosla, C., Tang, Y., Chen, A.Y., Schnarr, N.A. and Cane, D.E. Structure and mechanism of the 6-deoxyerythronolide B synthase. Annu. Rev. Biochem. 76 (2007) 195–221. [DOI] [PMID: 17328673]
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