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Chemical probes for the functionalization of polyketide intermediates.
Riva, Elena; Wilkening, Ina; Gazzola, Silvia; Li, W M Ariel; Smith, Luke; Leadlay, Peter F; Tosin, Manuela.
Affiliation
  • Riva E; Department of Chemistry, University of Warwick, Library Road, Coventry CV4 7AL (UK).
Angew Chem Int Ed Engl ; 53(44): 11944-9, 2014 Oct 27.
Article in En | MEDLINE | ID: mdl-25212788
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Discovery / Polyketides Language: En Journal: Angew Chem Int Ed Engl Year: 2014 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Discovery / Polyketides Language: En Journal: Angew Chem Int Ed Engl Year: 2014 Document type: Article