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


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:

SUBMITTER: Donia MS 

PROVIDER: S-EPMC4164201 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Donia Mohamed S MS   Cimermancic Peter P   Schulze Christopher J CJ   Wieland Brown Laura C LC   Martin John J   Mitreva Makedonka M   Clardy Jon J   Linington Roger G RG   Fischbach Michael A MA  

Cell 20140901 6


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 h  ...[more]

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