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Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR‐008
Author(s) -
Hu Zhihao,
Bao Kai,
Zhou Xiufen,
Zhou Qi,
Hopwood David A.,
Kieser Tobias,
Deng Zixln
Publication year - 1994
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1994.tb01276.x
Subject(s) - polyketide synthase , polyketide , biology , streptomyces , gene cluster , biosynthesis , polyene , gene , escherichia coli , streptomycetaceae , biochemistry , microbiology and biotechnology , genetics , bacteria , actinomycetales
Summary Genes for biosynthesis of a Streptomyces sp. FR‐008 heptaene macrolide antibiotic with antifungal and mosquito larvicidal activity were cloned in Escherichia coli using heterologous DNA probes. The cloned genes were implicated in heptaene biosynthiesis by gene replacement. The FR‐008 antibiotic contains a 38‐membered, poiyketide‐derived macrolide ring. Southern hybridization using probes encoding domains of the type i modular erythromycin polyketide synthase (PKS) showed that the Streptomyces sp. FR‐008 PKS gene cluster contains repeated sequences spanning c. 105 kb of contiguous DNA; assuming c. 5 kb for each PKS module, this is in striking agreement with the expectation for the 21‐step condensation process required for synthesis of the FR‐008 carbon chain. The methods developed for transformation and gene replacement in Streptomyces sp. FR‐008 make it possible to genetically manipulate polyene macrolide production, and may later lead to the biosynthesis of novel polyene macrolides.