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Chem Biol. 2010 Apr 23;17(4):402-11. doi: 10.1016/j.chembiol.2010.03.007.

Molecular cloning and heterologous expression of the dehydrophos biosynthetic gene cluster.

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  • 1Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Abstract

Dehydrophos is a vinyl phosphonate tripeptide produced by Streptomyces luridus with demonstrated broad-spectrum antibiotic activity. To identify genes necessary for biosynthesis of this unusual compound we screened a fosmid library of S. luridus for the presence of the phosphoenolpyruvate mutase gene, which is required for biosynthesis of most phosphonates. Integration of one such fosmid clone into the chromosome of S. lividans led to heterologous production of dehydrophos. Deletion analysis of this clone allowed identification of the minimal contiguous dehydrophos cluster, which contained 17 open reading frames (ORFs). Bioinformatic analyses of these ORFs are consistent with a proposed biosynthetic pathway that generates dehydrophos from phosphoenolpyruvate. The early steps of this pathway are supported by analysis of intermediates accumulated by blocked mutants and in vitro biochemical experiments.

PMID:
20416511
PMCID:
PMC2888486
DOI:
10.1016/j.chembiol.2010.03.007
[PubMed - indexed for MEDLINE]
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