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Updated: Apr 27, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Enediyne polyketide synthases stereoselectively reduce the β-ketoacyl intermediates to β-D-hydroxyacyl intermediates
Hui-Ming Ge1, Tingting Huang, Jeffrey D Rudolf
1Department of Chemistry, ‡Department of Molecular Therapeutics, and §Natural Products Library Initiatives, The Scripps Research Institute , Jupiter, Florida 33458, United States.
Abstract:
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 significantly as the chain length of the β-ketoacyl-SNAC substrate increases.
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