title: A thioesterase from an iterative fungal polyketide synthase shows macrocyclization and cross coupling activity and may play a role in controlling iterative cycling through product offloading.
abstract: Zearalenone, a fungal macrocyclic polyketide, is a member of the resorcylic acid lactone family. Herein, we characterize in vitro the thioesterase from PKS13 in zearalenone biosynthesis (Zea TE). The excised Zea TE catalyzes macrocyclization of a linear thioester-activated model of zearalenone. Zea TE also catalyzes the cross coupling of a benzoyl thioester with alcohols and amines. Kinetic characterization of the cross coupling is consistent with a ping-pong bi-bi mechanism, confirming an acyl-enzyme intermediate. Finally, the substrate specificity of the Zea TE indicates the TE may help control iterative cycling on PKS13 by rapidly offloading the final resorcylate-containing product.
authors.affiliation: Department of Chemistry, University of Ottawa, Ottawa, ON, Canada T1N 6N5.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Monica
authors.initials: M
authors.lastname: Wirz
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Boddy
mesh_terms: D055162:Biocatalysis; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004950:Esterases / Q000378:metabolism*; D005874:Gibberella / Q000201:enzymology*; D007700:Kinetics; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D048630:Polyketide Synthases; D004950:Esterases