title: Malonyl carba(dethia)- and malonyl oxa(dethia)-coenzyme A as tools for trapping polyketide intermediates.
abstract: In order to study intermediates in polyketide biosynthesis two nonhydrolyzable malonyl coenzyme A analogues were synthesised by a chemoenzymatic route. In these analogues the sulfur atom of CoA was replaced either by a methylene group (carbadethia analogue) or by an oxygen atom (oxadethia analogue). These malonyl-CoA analogues were found to compete with the natural extender unit malonyl-CoA and to trap intermediates from stilbene synthase, a type III polyketide synthase (PKS). From the reaction of stilbene synthase with its natural phenylpropanoid substrates, diketide, triketide and tetraketide species were successfully off-loaded and characterised by LC-MS. Moreover, the reactivity of the nonhydrolyzable analogues offers insights into the flexibility of substrate alignment in the PKS active site for efficient malonyl decarboxylation and condensation.
authors.affiliation: University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, UK. mt406@cam.ac.uk
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosin
authors.forename: Dieter
authors.initials: D
authors.lastname: Spiteller
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Spencer
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry*; D055162:Biocatalysis; D002853:Chromatography, Liquid; D018942:Macrolides / Q000737:chemistry*; D008316:Malonyl Coenzyme A / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D013058:Mass Spectrometry
chemical_list: D000227:Adenine Nucleotides; D000975:Antioxidants; D018942:Macrolides; C544091:malonylcarba(dethia)-coenzyme A; C544090:malonyloxa(dethia)-coenzyme A; D008316:Malonyl Coenzyme A; D000217:Acyltransferases; C022674:stilbene synthase