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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkholderia pseudomallei / genetics*
  • Burkholderia pseudomallei / metabolism*
  • Gene Expression
  • Genome, Bacterial / genetics*
  • HeLa Cells
  • Humans
  • Operon / genetics*