title: Enediyne polyketide synthases stereoselectively reduce the β-ketoacyl intermediates to β-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 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.
authors.affiliation: Department of Chemistry, ‡Department of Molecular Therapeutics, and §Natural Products Library Initiatives, The Scripps Research Institute , Jupiter, Florida 33458, United States.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Ge
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rudolf
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Lohman
authors.forename: Sheng-Xiong
authors.initials: SX
authors.lastname: Huang
authors.forename: Xun
authors.initials: X
authors.lastname: Guo
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D053281:Enediynes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D053281:Enediynes; D061065:Polyketides; D048630:Polyketide Synthases