866012-16-0Relevant academic research and scientific papers
An Unusual Dehydratase Acting on Glycerate and a Ketoreducatse Stereoselectively Reducing α-Ketone in Polyketide Starter Unit Biosynthesis
He, Hai-Yan,Yuan, Hua,Tang, Man-Cheng,Tang, Gong-Li
, p. 11315 - 11319 (2014)
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. Biochemical characterization of a dehydratase and a ketoreductase-like domain (DH?-KR?) in the loading module of FR901464 polyketide synthase revealed that DH? catalyzes the dehydration of an acyl carrier protein (ACP)-tethered glycerate to an ACP-linked pyruvate. The KR? domain then carries out α-ketone reduction to yield L-lactyl-S-ACP, which serves as a 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.
