Colibactin: understanding an elusive gut bacterial genotoxin

This highlight provides an overview of recent progress towards elucidating the structure, biosynthesis, and mode of action of colibactin, a genotoxic secondary metabolite synthesized by human gut bacteria. While isolating colibactin has been problematic, efforts to characterize its biosynthesis have provided critical information that has led to a rapid increase in our knowledge of this metabolite's structure and function. Major questions and gaps remain however, and the broader lessons learned from studying colibactin underscore central challenges to be faced in the genomics era of natural product research and in efforts to understand the human microbiome.