title: 6-Deoxyerythronolide B synthase thioesterase-catalyzed macrocyclization is highly stereoselective.
abstract: Macrocyclic polyketide natural products are an indispensable source of therapeutic agents. The final stage of their biosynthesis, macrocyclization, is catalyzed regio- and stereoselectively by a thioesterase. A panel of substrates were synthesized to test their specificity for macrocyclization by the erythromycin polyketide synthase TE (DEBS TE) in vitro. It was shown that DEBS TE is highly stereospecific, successfully macrocyclizing a 14-member ring substrate with an R configured O-nucleophile, and highly regioselective, generating exclusively the 14-member lactone over the 12-member lactone.
authors.affiliation: Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, ON, Canada T1N 6N5.
authors.forename: Atahualpa
authors.initials: A
authors.lastname: Pinto
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Horsman
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Boddy
mesh_terms: D002384:Catalysis; D003500:Cyclization; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry*; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D018942:Macrolides; C034277:6-deoxyerythronolide B; D004917:Erythromycin; D048630:Polyketide Synthases