title: In vivo evidence for a prodrug activation mechanism during colibactin maturation.
abstract: Releasing the cytopath: We have identified an N-myristoyl-D-asparagine (1) as the free N-terminal prodrug scaffold in cytopathogenic Escherichia coli strains expressing the colibactin gene cluster. Colibactin is released in vivo upon cleavage of precolibactin. We provide for the first time in vivo evidence of the prodrug-like release mechanism of colibactin.
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland HIPS, Helmholtz Centre for Infection Research HZI and Department of Pharmaceutical Biotechnology, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Bian
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Alberto
authors.initials: A
authors.lastname: Plaza
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrmann
authors.forename: Dominik
authors.initials: D
authors.lastname: Pistorius
authors.forename: A Francis
authors.initials: AF
authors.lastname: Stewart
authors.forename: Youming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
mesh_terms: D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000493:pharmacokinetics*
chemical_list: D010455:Peptides; D061065:Polyketides; D011355:Prodrugs; C569566:colibactin
keywords: E. coli Nissle; biosynthesis; colibactin; gene expression; prodrug maturation