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Cell. 2014 Sep 11;158(6):1402-1414. doi: 10.1016/j.cell.2014.08.032.

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

Author information

1
Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
3
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
4
The Genome Institute, Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA.
5
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: fischbach@fischbachgroup.org.

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.

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PMID:
25215495
PMCID:
PMC4164201
DOI:
10.1016/j.cell.2014.08.032
[Indexed for MEDLINE]
Free PMC Article

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