| Summary: | Colibactin is a secondary metabolite encoded by the <i>pks</i> gene island identified in several Enterobacteriaceae, including some pathogenic <i>Escherichia coli</i> (<i>E. coli</i>) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. <i>E. coli</i> harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of <i>pks</i><sup>+</sup> <i>E. coli</i> in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin’s structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.
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