In vivo evidence for a prodrug activation mechanism during colibactin maturation

Xiaoying Bian; Jun Fu; Alberto Plaza; Jennifer Herrmann; Dominik Pistorius; A Francis Stewart; Youming Zhang; Rolf Müller

doi:10.1002/cbic.201300208

In vivo evidence for a prodrug activation mechanism during colibactin maturation

Chembiochem. 2013 Jul 8;14(10):1194-7. doi: 10.1002/cbic.201300208. Epub 2013 Jun 6.

Authors

Xiaoying Bian¹, Jun Fu, Alberto Plaza, Jennifer Herrmann, Dominik Pistorius, A Francis Stewart, Youming Zhang, Rolf Müller

Affiliation

¹ 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.

PMID: 23744512
DOI: 10.1002/cbic.201300208

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.

Keywords: E. coli Nissle; biosynthesis; colibactin; gene expression; prodrug maturation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Escherichia coli / chemistry
Escherichia coli / genetics
Escherichia coli / metabolism*
Multigene Family
Peptides / chemistry
Peptides / genetics
Peptides / metabolism*
Polyketides / chemistry
Polyketides / metabolism*
Prodrugs / pharmacokinetics*

Substances

Peptides
Polyketides
Prodrugs
colibactin