Alteration of Polyketide Stereochemistry from anti to syn by a Ketoreductase Domain Exchange in a Type I Modular Polyketide Synthase Subunit

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• 作者：Clara H. Eng ; Satoshi Yuzawa ; George Wang ; Edward E. K. Baidoo ; Leonard Katz ; Jay D. Keasling
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：March 29, 2016
• 年：2016
• 卷：55
• 期：12
• 页码：1677-1680
• 全文大小：225K
• ISSN：1520-4995

文摘

Polyketide natural products have broad applications in medicine. Exploiting the modular nature of polyketide synthases to alter stereospecificity is an attractive strategy for obtaining natural product analogues with altered pharmaceutical properties. We demonstrate that by retaining a dimerization element present in LipPks1+TE, we are able to use a ketoreductase domain exchange to alter α-methyl group stereochemistry with unprecedented retention of activity and simultaneously achieve a novel alteration of polyketide product stereochemistry from anti to syn. The substrate promiscuity of LipPks1+TE further provided a unique opportunity to investigate the substrate dependence of ketoreductase activity in a polyketide synthase module context.