- Structure elucidation of colibactin and its DNA cross-links
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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.
- 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.
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- Development of a practical and scalable route for the preparation of the deacetoxytubuvaline (dTuv) fragment of pretubulysin and analogs
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We present herein a novel and convenient route for the scaling-up of the dTuv fragment of pretubulysin. The newly conceived chemical path involves a practical and efficient one-step procedure for the preparation of a key thiazole intermediate, followed by high-yielding Wittig olefination/reduction steps. The optimized route, starting from the inexpensive and non-toxic l-cysteine, encompasses five synthetic steps and only two chromatographic purifications, thus displaying a dramatically increased overall yield. The versatility of the proposed approach also provides new hints for the exploration of pretubulysin derivatives bearing diverse heterocyclic portions.
- Brindisi, Margherita,Maramai, Samuele,Grillo, Alessandro,Brogi, Simone,Butini, Stefania,Novellino, Ettore,Campiani, Giuseppe,Gemma, Sandra
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p. 920 - 923
(2016/02/05)
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