title: Chemical probes for the functionalization of polyketide intermediates.
abstract: A library of functionalized chemical probes capable of reacting with ketosynthase-bound biosynthetic intermediates was prepared and utilized to explore in vivo polyketide diversification. Fermentation of ACP mutants of S. lasaliensis in the presence of the probes generated a range of unnatural polyketide derivatives, including novel putative lasalocid A derivatives characterized by variable aryl ketone moieties and linear polyketide chains (bearing alkyne/azide handles and fluorine) flanking the polyether scaffold. By providing direct information on microorganism tolerance and enzyme processing of unnatural malonyl-ACP analogues, as well as on the amenability of unnatural polyketides to further structural modifications, the chemical probes constitute invaluable tools for the development of novel mutasynthesis and synthetic biology.
authors.affiliation: Department of Chemistry, University of Warwick, Library Road, Coventry CV4 7AL (UK).
authors.forename: Elena
authors.initials: E
authors.lastname: Riva
authors.forename: Ina
authors.initials: I
authors.lastname: Wilkening
authors.forename: Silvia
authors.initials: S
authors.lastname: Gazzola
authors.forename: W M Ariel
authors.initials: WM
authors.lastname: Li
authors.forename: Luke
authors.initials: L
authors.lastname: Smith
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosin
mesh_terms: D002384:Catalysis; D055808:Drug Discovery / Q000379:methods*; D061065:Polyketides / Q000737:chemistry*
chemical_list: D061065:Polyketides
keywords: biosynthesis; drug discovery; enzymes; polyketides; synthetic methods