Comparative Metabolomics and Structural Characterizations Illuminate Colibactin Pathway-Dependent Small Molecules

详细信息    查看全文

• 作者：Maria I. Vizcaino ; Philipp Engel ; Eric Trautman ; Jason M. Crawford
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：July 2, 2014
• 年：2014
• 卷：136
• 期：26
• 页码：9244-9247
• 全文大小：294K
• ISSN：1520-5126

文摘

The gene cluster responsible for synthesis of the unknown molecule 鈥渃olibactin鈥?has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported. Here we implemented a comparative metabolomics and targeted structural network analyses approach to identify a catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The structures of 10 pathway-dependent small molecules are proposed based on structural characterizations and network relationships. The network will provide a roadmap for the structural and functional elucidation of a variety of other small molecules encoded by the pathway. From the characterized small molecule set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist activities are presented.