A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.

Mohamed S. Donia, Peter Cimermancic, Christopher J. Schulze, Laura C. Wieland Brown, John Martin, Makedonka Mitreva, Jon Clardy, Roger G. Linington, Michael A. Fischbach

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297 Scopus citations

Abstract

In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:

Original languageEnglish (US)
Pages (from-to)1402-1414
Number of pages13
JournalCell
Volume158
Issue number6
DOIs
StatePublished - Sep 11 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Donia, M. S., Cimermancic, P., Schulze, C. J., Wieland Brown, L. C., Martin, J., Mitreva, M., Clardy, J., Linington, R. G., & Fischbach, M. A. (2014). A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell, 158(6), 1402-1414. https://doi.org/10.1016/j.cell.2014.08.032