State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China).
Angew Chem Int Ed Engl. 2014 Oct 13;53(42):11315-9. doi: 10.1002/anie.201406602. Epub 2014 Aug 27.
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.
聚酮合酶 (PKSs) 通常采用酮还原酶 (KR) 催化β-酮基的还原，然后采用脱水酶 (DH) 使α-和β-碳原子之间形成双键。本文对 FR901464 生物合成中涉及的 DH*-KR进行了表征：DH作用于甘油酰基-S-酰基载体蛋白 (ACP) 生成 ACP 连接的丙酮酸；随后 KR*还原α-酮基生成 L-乳酸基-S-ACP，作为聚酮生物合成的起始单元。遗传和生化证据支持参与放线菌酮生物合成的类似途径。这些结果不仅鉴定了作用于不同底物的新型 PKS 结构域，还为工程化 PKS 起始途径或生物催化提供了更多选择。
