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Metabolites from the induced expression of cryptic single operons found in the genome of Burkholderia pseudomallei
Authors:Biggins John B  Liu Xiaofei  Feng Zhiyang  Brady Sean F
Institution: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.
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