Structure elucidation of colibactin and its DNA cross-links.
Mengzhao XueChung Sub KimAlan R HealyKevin M WernkeZhixun WangMadeline C FrischlingEmilee E ShineWeiwei WangSeth B HerzonJason M CrawfordPublished in: Science (New York, N.Y.) (2019)
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.
Keyphrases
- escherichia coli
- tandem mass spectrometry
- high performance liquid chromatography
- gas chromatography
- liquid chromatography
- ultra high performance liquid chromatography
- simultaneous determination
- high resolution
- dna methylation
- circulating tumor
- cystic fibrosis
- transcription factor
- copy number
- single molecule
- multidrug resistant
- staphylococcus aureus
- high resolution mass spectrometry
- deep learning
- induced pluripotent stem cells
- data analysis
- klebsiella pneumoniae