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

By Mohamed S. Donia, Peter Cimermancic, C. Schulze, Laura C. Wieland Brown, John C. Martin, M. Mitreva, Jon Clardy, Roger G. Linington, Michael A. Fischbach. Cell, 2014

650 citations recorded by the source corpus.

SUMMARY 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 new 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.

Subfields: Food Science, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/bfffacfdd182b9595c5977f1e3b3e01b5511eef3

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In Food Science

  1. Eric G. Pamer
  2. Michael A. Fischbach
  3. Mohamed S. Donia

In Molecular Biology

  1. Mohamed S. Donia
  2. Y. Taur
  3. Eric G. Pamer
  4. Michael A. Fischbach

In Pharmacology

  1. Mohamed S. Donia
  2. Michael A. Fischbach

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