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J Am Chem Soc. 2013 Nov 27;135(47):17906-12. doi: 10.1021/ja408683p. Epub 2013 Nov 14.

Discovery and synthetic refactoring of tryptophan dimer gene clusters from the environment.

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

Abstract

Here we investigate bacterial tryptophan dimer (TD) biosynthesis by probing environmental DNA (eDNA) libraries for chromopyrrolic acid (CPA) synthase genes. Functional and bioinformatics analyses of TD clusters indicate that CPA synthase gene sequences diverge in concert with the functional output of their respective clusters, making this gene a powerful tool for guiding the discovery of novel TDs from the environment. Twelve unprecedented TD biosynthetic gene clusters that can be arranged into five groups (A-E) based on their ability to generate distinct TD core substructures were recovered from eDNA libraries. Four of these groups contain clusters from both cultured and culture independent studies, while the remaining group consists entirely of eDNA-derived clusters. The complete synthetic refactoring of a representative gene cluster from the latter eDNA specific group led to the characterization of the erdasporines, cytotoxins with a novel carboxy-indolocarbazole TD substructure. Analysis of CPA synthase genes in crude eDNA suggests the presence of additional TD gene clusters in soil environments.

PMID:
24171465
[PubMed - indexed for MEDLINE]
PMCID:
PMC3878720
Free PMC Article
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