1. Academic Validation
  2. Structure elucidation of colibactin and its DNA cross-links

Structure elucidation of colibactin and its DNA cross-links

  • Science. 2019 Sep 6;365(6457):eaax2685. doi: 10.1126/science.aax2685.
Mengzhao Xue  # 1 Chung Sub Kim  # 1 2 Alan R Healy 1 2 Kevin M Wernke 1 Zhixun Wang 1 Madeline C Frischling 1 Emilee E Shine 2 3 Weiwei Wang 4 5 Seth B Herzon 6 7 Jason M Crawford 6 2 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • 2 Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
  • 3 Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA.
  • 4 Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.
  • 5 W. M. Keck Biotechnology Resource Laboratory, Yale School of Medicine, New Haven, CT 06510, USA.
  • 6 Department of Chemistry, Yale University, New Haven, CT 06520, USA. [email protected] [email protected].
  • 7 Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA.
  • # Contributed equally.
Abstract

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.

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