An Unusual Dehydratase Acting on Glycerate and a Ketoreducatse Stereoselectively Reducing α-Ketone in Polyketide Starter Unit Biosynthesis†
Dr. Hai-Yan He
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorDr. Hua Yuan
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorDr. Man-Cheng Tang
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorCorresponding Author
Prof. Dr. Gong-Li Tang
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237 (China)
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)Search for more papers by this authorDr. Hai-Yan He
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorDr. Hua Yuan
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorDr. Man-Cheng Tang
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Search for more papers by this authorCorresponding Author
Prof. Dr. Gong-Li Tang
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)
Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237 (China)
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)Search for more papers by this authorWe thank Prof. Zixin Deng’s Lab at Shanghai JiaoTong University for support in obtaining MS data. This work was financially supported by grants from the 973 Program (2010CB833200) and NNSFC (31200054 and 31330003).
Abstract
Polyketide synthases (PKSs) usually employ a ketoreductase (KR) to catalyze the reduction of a β-keto group, followed by a dehydratase (DH) that drives the dehydration to form a double bond between the α- and β-carbon atoms. Herein, a DH*-KR* involved in FR901464 biosynthesis was characterized: DH* acts on glyceryl-S-acyl carrier protein (ACP) to yield ACP-linked pyruvate; subsequently KR* reduces α-ketone that yields L-lactyl-S-ACP as starter unit for polyketide biosynthesis. Genetic and biochemical evidence was found to support a similar pathway that is involved in the biosynthesis of lankacidins. These results not only identified new PKS domains acting on different substrates, but also provided additional options for engineering the PKS starter pathway or biocatalysis.
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