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Mechanism and engineering of polyketide chain initiation in fredericamycin biosynthesis.

ABSTRACT: The ability to incorporate atypical primer units through the use of dedicated initiation polyketide synthase (PKS) modules offers opportunities to expand the molecular diversity of polyketide natural products. Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties. We also exploit this PKS module for the design and in vivo biosynthesis of unusually primed analogues of a representative polyketide product, thereby emphasizing its utility to the metabolic engineer.

SUBMITTER: Das A

PROVIDER: S-EPMC2904946 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Mechanism and engineering of polyketide chain initiation in fredericamycin biosynthesis.

Das Abhirup A Szu Ping-Hui PH Fitzgerald Jay T JT Khosla Chaitan C

Journal of the American Chemical Society 20100701 26

The ability to incorporate atypical primer units through the use of dedicated initiation polyketide synthase (PKS) modules offers opportunities to expand the molecular diversity of polyketide natural products. Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties. We also exploit this PKS module for the design and in vivo biosynthesis of unusually primed analogues of a representative polyketide pr ...[more]

PMID: 20540492

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