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August 8, 2019Science271 citations

Structure elucidation of colibactin and its DNA cross-links

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MXMengzhao XueCKChung Sub KimAHAlan R. Healy

Key Points

  • This research aims to structurally elucidate colibactin and investigate its connections to colorectal cancer severity.
  • Utilized genetics and chemical synthesis to characterize colibactin's structure.
  • Employed isotope labeling and tandem mass spectrometry for detailed analysis.
  • Integrated biosynthetic and cellular biology data to refine structural interpretation.
  • Identified colibactin's structure for the first time, revealing its DNA cross-linking capability.
  • The structural assignment aligns with known biosynthetic pathways, hinting at the functions of unidentified enzymes in the gene cluster.

Abstract

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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Cite This Study

Xue et al. (2019) studied this question.

synapsesocial.com/papers/6a327edc98d9c97b83e45a83https://doi.org/10.1126/science.aax2685
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