美国耶鲁大学Jason M. Crawford和Seth B. Herzon研究组合作阐明了大肠杆菌素的结构以及大肠杆菌素如何与DNA交联。2019年9月6日出版的《科学》发表了这项成果。

研究人员结合使用遗传学、同位素标记、串联质谱和化学合成来推测大肠杆菌素的结构。研究人员解析的结构分配解释了所有已知的生物合成和细胞生物学数据，并提出了大肠杆菌素基因簇中未知酶的作用。

研究人员介绍，大肠杆菌素是由一些基因毒性的的肠道大肠杆菌菌产生的复杂次级代谢产物。 产生大肠杆菌素的细菌的存在与人类结肠直肠癌的频率和严重程度相关。 然而，由于大肠杆菌素尚未被分离或被解析结构，因此研究产大肠杆菌素的细菌在人体肠道中的生理作用是十分困难的。

附：英文原文

Title: Structure elucidation of colibactin and its DNA cross-links

Author: 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

Issue&Volume: Volume 365 Issue 6457

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.

DOI: 10.1126/science.aax2685

Source: https://science.sciencemag.org/content/365/6457/eaax2685