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

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


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:

MeSH terms

  • Amino Acid Sequence
  • Bacteria / chemistry*
  • Bacteria / classification
  • Bacteria / genetics*
  • Bacteria / metabolism
  • Biosynthetic Pathways
  • Gastrointestinal Tract / microbiology
  • Humans
  • Metagenomics / methods*
  • Microbiota*
  • Molecular Sequence Data
  • Mouth / microbiology
  • Multigene Family
  • Peptide Biosynthesis, Nucleic Acid-Independent
  • Polyketides / analysis


  • Polyketides