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Colibactin is a polyketide/nonribosomal peptide produced by Escherichia coli strains that harbor the pks island. This toxin induces DNA double-strand breaks and DNA interstrand cross-links in infected eukaryotic cells. Colibactin-producing strains are found associated with colorectal cancer biopsy specimens and promote intestinal tumor progression...
The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic Enterobacteria, and is associated with colon cancer development and acute systemic infections. The colibactin biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase ClbA. We recently evidenced that two master regulators of bacterial i...
Highly pathogenic Escherichia coli strains that belong to the phylogenetic group B2 have developed a greater ability to acquire iron (heme receptor and numerous siderophores), to produce the genotoxin colibactin and to synthesize antimicrobial siderophore-microcins. There is an increased prevalence of these E. coli strains over the last 30 years in...
L'îlot génomique pks code une machinerie de biosynthèse complexe synthétisant la colibactine, une génotoxine produite par certaines souches de Escherichia coli. Cette génotoxine induit des cassures double-brin de l'ADN sur les cellules eucaryotes in vitro et in vivo. La colibactine n'est pas une protéine, mais un métabolite secondaire de type polyc...
The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by i...
The genotoxin colibactin synthesized by Escherichia coli is a secondary metabolite belonging to the chemical family of hybrid polyketide/non-ribosomal peptide compounds. It is produced by a complex biosynthetic assembly line encoded by the pks pathogenicity island. The presence of this large cluster of genes in the E. coli genome is invariably asso...
The as-yet unidentified E. coli metabolite colibactin induces DNA damage in eukaryotic cells and promotes tumorigenesis. Its wide distribution in pathogenic and probiotic strains has raised great interest in the structure and biogenesis of colibactin. Here we show that biosynthesis involves a rare aminomalonyl unit used as building block.
In Escherichia coli, the biosynthetic pathways of several small iron-scavenging molecules known as siderophores (enterobactin, salmochelins and yersiniabactin) and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl transferase (PPTase). Only two PPTases have been clearly identified: EntD and ClbA. The gene coding for EntD is...