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Enediyne Polyketide Synthases Stereoselectively Reduce the 尾-Ketoacyl Intermediates to 尾-d-Hydroxyacyl Intermediates in Enediyne Core Biosynthesis
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文摘
PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative 尾-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with 尾-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the 尾-ketoacyl-SNACs stereoselectively, all affording the corresponding 尾-d-hydroxyacyl-SNACs, and the catalytic efficiencies (kcat/KM) of the KRs increased significantly as the chain length of the 尾-ketoacyl-SNAC substrate increases.

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