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    Chem Biol. 2003 Dec;10(12):1225-32.

    Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster.

    Source

    Hans-Knoell-Institute for Natural Products Research, Department of Bioorganic Synthesis, Beutenbergstr 11a, D-07745 Jena, Germany.

    Abstract

    Analysis of the type I modular polyketide synthase (PKS) involved in the biosynthesis of the rare nitroaryl polyketide metabolite aureothin (aur) from Streptomyces thioluteus HKI-227 has revealed only four modules to catalyze the five polyketide chain extensions required. By heterologous expression of the aur PKS cluster, direct evidence was obtained that these modules were sufficient to support aureothin biosynthesis. It appears that one module catalyzes two successive cycles of chain extension, one of the first examples of a PKS in which such iteration or "stuttering" is required to produce the normal polyketide product. In addition, lack of a specified loading domain implicates a novel PKS priming mechanism involving the unique p-nitrobenzoate starter unit. The 27 kb aur gene cluster also encodes a novel N-oxidase, which may represent the first member of a new family of such enzymes.

    PMID:
    14700630
    [PubMed - indexed for MEDLINE]

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