Structure elucidation of colibactin and its DNA cross-links

Science. 2019 Sep 6;365(6457):eaax2685. doi: 10.1126/science.aax2685. Epub 2019 Aug 8.


Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA Adducts / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Isotope Labeling
  • Mutation
  • Peptide Hydrolases / genetics
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism
  • Polyketides / chemistry*
  • Polyketides / metabolism
  • Protein Conformation
  • Secondary Metabolism
  • Tandem Mass Spectrometry


  • DNA Adducts
  • Escherichia coli Proteins
  • Peptides
  • Polyketides
  • colibactin
  • ClbP protein, E coli
  • Peptide Hydrolases