title: Cis-Double bond formation by thioesterase and transfer by ketosynthase in FR901464 biosynthesis.
abstract: Modular polyketide synthases (PKSs) are well known to use ketosynthase (KS)-driven carbon-carbon bond formation, dehydratase-mediated dehydration to form double bonds, and product release by thioesterase (TE), all of which are regarded as the "canonical" roles for most polyketide biosyntheses. FR901464 is biosynthesized by a complex acyltransferase-less PKS system involving a nonterminal TE domain and several mutated KS domains. Here we demonstrate that this TE catalyzes the dehydration of the polyketide intermediate to yield a cis-double bond and a mutated KS transfers the nascent polyketide chain with only a cis-double bond to the downstream acyl carrier protein. These findings not only provide new insights into different enzymatic functions of PKS domains but also suggest an alternative strategy for cis-double bond formation during the polyketide assembly line.
authors.affiliation: State Key Laboratory of Bio-organic 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: Man-Cheng
authors.initials: MC
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
mesh_terms: D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry*; D048630:Polyketide Synthases / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: C104486:FR 901464; D011714:Pyrans; D013141:Spiro Compounds; D002244:Carbon; D048630:Polyketide Synthases