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Enediyne polyketide synthases stereoselectively reduce the ?-ketoacyl intermediates to ?-D-hydroxyacyl intermediates in enediyne core biosynthesis.

ABSTRACT: PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative ?-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with ?-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the ?-ketoacyl-SNACs stereoselectively, all affording the corresponding ?-D-hydroxyacyl-SNACs, and the catalytic efficiencies (k(cat)/K(M)) of the KRs increased significantly as the chain length of the ?-ketoacyl-SNAC substrate increases.

SUBMITTER: Ge HM

PROVIDER: S-EPMC4144755 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Enediyne polyketide synthases stereoselectively reduce the β-ketoacyl intermediates to β-D-hydroxyacyl intermediates in enediyne core biosynthesis.

Ge Hui-Ming HM Huang Tingting T Rudolf Jeffrey D JD Lohman Jeremy R JR Huang Sheng-Xiong SX Guo Xun X Shen Ben B

Organic letters 20140714 15

PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative β-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with β-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the β-ketoacyl-SNACs stereoselectively, all affording the corresponding β-D-hydroxyacyl-SNACs, and the catalytic efficiencies (k(cat)/K(M)) of the KRs increased sign ...[more]

PMID: 25019332

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