title: An unusual dehydratase acting on glycerate and a ketoreducatse stereoselectively reducing α-ketone in polyketide starter unit biosynthesis.
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.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China).
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: He
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
authors.forename: Man-Cheng
authors.initials: MC
authors.lastname: Tang
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D053898:Biosynthetic Pathways; D004926:Escherichia coli / Q000378:metabolism*; D005988:Glyceric Acids / Q000378:metabolism*; D006836:Hydro-Lyases / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism; D018942:Macrolides / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism; D011714:Pyrans / Q000378:metabolism; D013141:Spiro Compounds / Q000378:metabolism; D013302:Streptomyces / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; C104486:FR 901464; D005988:Glyceric Acids; D007659:Ketones; D018942:Macrolides; D011714:Pyrans; D013141:Spiro Compounds; C008250:lankacidins; C042971:glyceric acid; D048630:Polyketide Synthases; D006836:Hydro-Lyases
keywords: FR901464; PKS starter; dehydratase; ketoreductase; α-ketone reduction