Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137.
Nigericin was among the first polyether ionophores to be discovered, but its biosynthesis remains obscure. The biosynthetic gene cluster for nigericin has been serendipitously cloned from Streptomyces sp. DSM4137, and deletion of this gene cluster abolished the production of both nigericin and the closely related metabolite abierixin. Detailed comparison of the nigericin biosynthetic genes with their counterparts in the biosynthetic clusters for other polyketides has prompted a significant revision of the proposed common pathway for polyether biosynthesis. In particular, we present evidence that in nigericin, nanchangmycin, and monensin, an unusual ketosynthase-like protein, KSX, transfers the initially formed linear polyketide chain to a discrete acyl carrier protein, ACPX, for oxidative cyclization. Consistent with this, deletion of either monACPX or monKSX from the monensin gene cluster effectively abolished monensin A biosynthesis.
Harvey
Barbara M
BM
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Mironenko
Tatiana
T
Sun
Yuhui
Y
Hong
Hui
H
Deng
Zixin
Z
Leadlay
Peter F
PF
Weissman
Kira J
KJ
Haydock
Stephen F
SF
D000215:Acylation; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D003001:Cloning, Molecular; D003500:Cyclization; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009550:Nigericin / Q000096:biosynthesis* / Q000737:chemistry; D016366:Open Reading Frames; D010084:Oxidation-Reduction; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D048630:Polyketide Synthases; D009550:Nigericin