EC - 6-deoxyerythronolide-B synthase

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IntEnz Enzyme Nomenclature


Accepted name:
6-deoxyerythronolide-B synthase
Other names:
erythronolide-condensing enzyme
malonyl-CoA:propionyl-CoA malonyltransferase (cyclizing)
malonyl-CoA:propanoyl-CoA malonyltransferase (cyclizing)
erythronolide synthase
deoxyerythronolide B synthase
6-deoxyerythronolide B synthase
Systematic name:
propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing)



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

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0047879
CAS Registry Number: 87683-77-0


  1. Omura, S. and Nakagawa, A.
    Biosynthesis of 16-membered macrolide antibiotics.
    Antibiotics 4 : 175-192 (1981).
  2. Roberts, G. and Leadley, P.F.
    Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus.
    Biochem. Soc. Trans. 12 : 642-643 (1984).
  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 : 1790-1792 (2001). [PMID: 11230695]
  4. Tsai, S.-C., Miercke, L.J.W., Krucinski, J., Gokhale, R., Chen, J.C.-H., 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 : 14808-14813 (2001). [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 : 195-221 (2007). [PMID: 17328673]

[EC created 1989, modified 2008]