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. 2003 Jul 2;125(26):7818-9.
doi: 10.1021/ja034781q.

The complete gene cluster of the antitumor agent gilvocarcin V and its implication for the biosynthesis of the gilvocarcins

Carsten Fischer  1 , Fredilyn Lipata, Jürgen Rohr
Affiliations

The complete gene cluster of the antitumor agent gilvocarcin V and its implication for the biosynthesis of the gilvocarcins

Carsten Fischer et al. J Am Chem Soc. .

Abstract

Gilvocarcin V, an antitumor agent produced by the bacterium Streptomyces griseoflavus Gö 3592, is the most studied representative of the distinct family of benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotics, which show excellent antitumor activity and a remarkably low toxicity. Its biosynthesis contains many intriguing steps, including an oxidative rearrangement, the C-glycosylation, and the generation of a vinyl side chain. These steps all contribute to structural elements of the drug, which are essential for its biological activity, but only poorly understood. Herein we report the cloning and characterization of the gilvocarcin (gil) gene cluster from S. griseoflavus Gö 3592, and its heterologous expression in a foreign host (S. lividans). This is the first reported gene cluster encoding the biosynthesis of a benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotic, which not only provides insights regarding the biosynthesis of gilvocarcin V but also lays the foundation for the detailed studies of its intriguing biosynthetic steps and possibly for the generation of gilvocarcin analogues with improved biological activities through combinatorial biosynthesis.

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Figures

Scheme 1
Scheme 1
The Complete Gilvocarcin Gene Cluster and the Postulated Biosynthetic Sequence of Eventsa a Black genes code for the PKS and associated enzymes, gray genes for post-PKS tailoring steps, and white genes for regulation, transport, resistance, and enzymes of unknown function.
Scheme 2
Scheme 2
Proposed Involvement of Enzymes of the Gilvocarcin Pathway in the Biosynthesis of GV’s D-Fucofuranose Moiety
See this image and copyright information in PMC

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