Structure elucidation of colibactin and its DNA cross-links

• Published in: Science (American Association for the Advancement of Science) Vol. 365; no. 6457; p. 1000
• Main Authors: Xue, Mengzhao, Kim, Chung Sub, Healy, Alan R., Wernke, Kevin M., Wang, Zhixun, Frischling, Madeline C., Shine, Emilee E., Wang, Weiwei, Herzon, Seth B., Crawford, Jason M.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 06.09.2019; The American Association for the Advancement of Science
• Subjects: Alkylation; Animal models; Bacteria; Bases (nucleic acids); Biological activity; Biosynthesis; Cancer; Carcinogens; Cell culture; Chemical synthesis; Chemistry; Coliforms; Colorectal cancer; Colorectal carcinoma; Correlation; Crosslinking; Cyclopropane; Cytology; Deoxyribonucleic acid; DNA; DNA Adducts - chemistry; DNA biosynthesis; DNA damage; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Genetics; Genome editing; Genomes; Genotoxicity; Interdisciplinary Approach; Interdisciplinary aspects; Intermediates; Intestinal microflora; Isotope Labeling; Labeling; Mass spectrometry; Mass spectroscopy; Metabolites; Metabolomics; Microbiomes; Mutation; Natural products; Nucleotides; Organic chemistry; Peptide Hydrolases - genetics; Peptides - chemistry; Peptides - genetics; Peptides - metabolism; Phenotypes; Physiological effects; Physiology; Polyketides - chemistry; Polyketides - metabolism; Precursors; Protein Conformation; RESEARCH ARTICLE SUMMARY; Researchers; Scientific imaging; Secondary Metabolism; Spectroscopy; Strains (organisms); Structure-function relationships; Tandem Mass Spectrometry; Warheads

Strains of the human gut bacterium Escherichia coli carrying the clb gene cluster produce a secondary metabolite dubbed colibactin and have been provocatively linked to colorectal cancer in some models. Colibactin has been difficult to isolate in full, but pieces of the structure have been worked ou...