title: ClbP is a prototype of a peptidase subgroup involved in biosynthesis of nonribosomal peptides.
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.
authors.affiliation: Laboratoire 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.
authors.forename: Damien
authors.initials: D
authors.lastname: Dubois
authors.affiliation: INSERM U1043, Toulouse F-31076, France; Centre National de Recherche Scientifique, U5282, Toulouse F-31076, France; Institut National de Recherche Agronomique, Unité Sous Contrat, Toulouse F-31076, France; Université Paul Sabatier-Toulouse III, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31076, France; Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Service de Bactériologie-Hygiène, Toulouse F-31059, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baron
authors.affiliation: Institut National de Recherche Agronomique, Clermont Université, JE 2526 Université d'Auvergne, Unité Sous Contrat 2018, Clermont-Ferrand F-63001, France.
authors.forename: Antony
authors.initials: A
authors.lastname: Cougnoux
authors.affiliation: Laboratoire 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.
authors.forename: Julien
authors.initials: J
authors.lastname: Delmas
authors.affiliation: Institut National de Recherche Agronomique, Clermont Université, JE 2526 Université d'Auvergne, Unité Sous Contrat 2018, Clermont-Ferrand F-63001, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pradel
authors.affiliation: INSERM U1043, Toulouse F-31076, France; Centre National de Recherche Scientifique, U5282, Toulouse F-31076, France; Institut National de Recherche Agronomique, Unité Sous Contrat, Toulouse F-31076, France; Université Paul Sabatier-Toulouse III, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31076, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Boury
authors.affiliation: INSERM U990, Clermont-Ferrand, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bouchon
authors.affiliation: Institut National de Recherche Agronomique, Clermont Université, JE 2526 Université d'Auvergne, Unité Sous Contrat 2018, Clermont-Ferrand F-63001, France.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Bringer
authors.affiliation: INSERM U1043, Toulouse F-31076, France; Centre National de Recherche Scientifique, U5282, Toulouse F-31076, France; Institut National de Recherche Agronomique, Unité Sous Contrat, Toulouse F-31076, France; Université Paul Sabatier-Toulouse III, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31076, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Nougayrède
authors.affiliation: INSERM U1043, Toulouse F-31076, France; Centre National de Recherche Scientifique, U5282, Toulouse F-31076, France; Institut National de Recherche Agronomique, Unité Sous Contrat, Toulouse F-31076, France; Université Paul Sabatier-Toulouse III, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-31076, France; Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Service de Bactériologie-Hygiène, Toulouse F-31059, France. Electronic address: e.oswald@envt.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
authors.affiliation: Laboratoire 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. Electronic address: rbonnet@chu-clermontferrand.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005816:Genetic Complementation Test; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D048630:Polyketide Synthases; C577770:ClbP protein, E coli; D010447:Peptide Hydrolases