ClbP is a prototype of a peptidase subgroup involved in biosynthesis of nonribosomal peptides
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Updated: May 30, 2026

Bacterial Peptide Display for the Selection of Novel Biotinylating Enzymes
Published on: October 3, 2019
Damien Dubois1, Olivier Baron2, Antony Cougnoux3
1Laboratoire de Bactériologie Clinique, Centre Hospitalier de Clermont-Ferrand, Clermont-Ferrand F-63003, France; Institut National de Recherche Agronomique, Clermont Université, JE 2526 Université d'Auvergne, Unité Sous Contrat 2018, Clermont-Ferrand F-63001, France.
Abstract:
The pks genomic island of Escherichia coli encodes polyketide (PK) and nonribosomal peptide (NRP) synthases that allow assembly of a putative hybrid PK-NRP compound named colibactin that induces DNA double-strand breaks in eukaryotic cells. The pks-encoded machinery harbors an atypical essential protein, ClbP. ClbP crystal structure and mutagenesis experiments revealed a serine-active site and original structural features compatible with peptidase activity, which was detected by biochemical assays. Ten ClbP homologs were identified in silico in NRP genomic islands of closely and distantly related bacterial species. All tested ClbP homologs were able to complement a clbP-deficient E. coli mutant. ClbP is therefore a prototype of a new subfamily of extracytoplasmic peptidases probably involved in the maturation of NRP compounds. Such peptidases will be powerful tools for the manipulation of NRP biosynthetic pathways.
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