期刊
CELL
卷 158, 期 6, 页码 1402-1414出版社
CELL PRESS
DOI: 10.1016/j.cell.2014.08.032
关键词
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资金
- Howard Hughes Medical Institute Predoctoral Fellowship
- NIH [TW006634, OD007290, AI101018, AI101722, GM081879]
- Medical Research Program Grant from the W.M. Keck Foundation
- Fellowship for Science and Engineering from the David and Lucile Packard Foundation
- DARPA [HR0011-12-C-0067]
- Program for Breakthrough Biomedical Research
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.
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