Chemical probes for the functionalization of polyketide intermediates.
Angew Chem Int Ed Engl
; 53(44): 11944-9, 2014 Oct 27.
Article
em 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 inâ
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 lasalocidâ
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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MEDLINE
Assunto principal:
Descoberta de Drogas
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Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2014
Tipo de documento:
Article