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An Unusual Dehydratase Acting on Glycerate and a Ketoreducatse Stereoselectively Reducing α‐Ketone in Polyketide Starter Unit Biosynthesis
Author(s) -
He HaiYan,
Yuan Hua,
Tang ManCheng,
Tang GongLi
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201406602
Subject(s) - polyketide , dehydratase , biosynthesis , chemistry , ketone , stereochemistry , biocatalysis , starter , biochemistry , metabolic engineering , acyl carrier protein , enzyme , organic chemistry , catalysis , reaction mechanism , food science
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.