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J Am Chem Soc. 2011 Feb 16;133(6):1638-41. doi: 10.1021/ja1087369. Epub 2011 Jan 19.

Metabolites from the induced expression of cryptic single operons found in the genome of Burkholderia pseudomallei.

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1
Laboratory for Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.

Abstract

Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium Burkholderia pseudomallei . Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways.

PMID:
21247113
PMCID:
PMC4872597
DOI:
10.1021/ja1087369
[Indexed for MEDLINE]
Free PMC Article
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