Structure elucidation of colibactin and its DNA cross-links

Mengzhao Xue, Chung Sub Kim, Alan R. Healy, Kevin M. Wernke, Zhixun Wang, Madeline C. Frischling, Emilee E. Shine, Weiwei Wang, Seth B. Herzon, Jason M. Crawford

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numberaax2685
JournalScience
Volume365
Issue number6457
DOIs
StatePublished - Sep 6 2019

ASJC Scopus subject areas

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    Xue, M., Kim, C. S., Healy, A. R., Wernke, K. M., Wang, Z., Frischling, M. C., Shine, E. E., Wang, W., Herzon, S. B., & Crawford, J. M. (2019). Structure elucidation of colibactin and its DNA cross-links. Science, 365(6457), [aax2685]. https://doi.org/10.1126/science.aax2685