title: Metabolic coupling of dehydration and decarboxylation in the curacin A pathway: functional identification of a mechanistically diverse enzyme pair.
abstract: This study describes the functional identification of a pair of mechanistically diverse enzymes that catalyze the successive dehydration (CurE ECH1) and decarboxylation (CurF ECH2) of (S)-HMG-ACP to generate a 3-methylcrotonyl-ACP intermediate, the presumed precursor of the cyclopropyl ring in curacin A. The reactions catalyzed by ECH1 and ECH2 are found in a broad cross-section of microbial natural product gene clusters and participate in the introduction of carbon chain branch points and functional group diversity as key steps in the HMG-CoA synthase mediated addition of C-2 from acetate to the beta-carbonyl group of polyketide chains.
authors.affiliation: Life Sciences Institute, Department of Medicinal Chemistry, Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Gu
authors.forename: Junyong
authors.initials: J
authors.lastname: Jia
authors.forename: Haichuan
authors.initials: H
authors.lastname: Liu
authors.forename: Kristina
authors.initials: K
authors.lastname: Håkansson
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D000458:Cyanobacteria / Q000201:enzymology*; D003521:Cyclopropanes / Q000737:chemistry / Q000378:metabolism*; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003521:Cyclopropanes; D004798:Enzymes; D013844:Thiazoles; C095843:curacin A