A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.
Author: Donia MS1, Cimermancic P1, Schulze CJ2, Wieland Brown LC3, Martin J4, Mitreva M4, Clardy J5, Linington RG2, Fischbach MA6.
Affiliation:
1Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. 2Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. 3Department of Chemistry, Indiana University, Bloomington, IN 47405, USA. 4The Genome Institute, Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA. 5Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. 6Department 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.
Conference/Journal: Cell
Date published: 2014 Sep 11
Other:
Volume ID: 158 , Issue ID: 6 , Pages: 1402-14 , Special Notes: doi: 10.1016/j.cell.2014.08.032 , Word Count: 160
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:
Copyright © 2014 Elsevier Inc. All rights reserved.
PMID: 25215495 [PubMed - indexed for MEDLINE] PMCID: PMC4164201 [Available on 2015/9/11]
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