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Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the <i>pks</i> genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the <i>pks</i> island is found in members of the family <i>Enterobacteriaceae</i> (mainly <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The <i>pks</i> island is mainly observed in B2 phylogroup <i>E. coli</i> strains, which include extra-intestinal pathogenic <i>E. coli</i> strains, and <i>pks</i><i>E. coli</i> are over-represented in biopsies isolated from colorectal cancer. In addition, <i>pks</i><i>E. coli</i> bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the <i>pks</i> island, and summarize what is currently known about its synthesis and its structure.