title: Analysis of 51 cyclodipeptide synthases reveals the basis for substrate specificity.
abstract: Cyclodipeptide synthases (CDPSs) constitute a family of peptide bond-forming enzymes that use aminoacyl-tRNAs for the synthesis of cyclodipeptides. Here, we describe the activity of 41 new CDPSs. We also show that CDPSs can be classified into two main phylogenetically distinct subfamilies characterized by specific functional subsequence signatures, named NYH and XYP. All 11 previously characterized CDPSs belong to the NYH subfamily, suggesting that further special features may be yet to be discovered in the other subfamily. CDPSs synthesize a large diversity of cyclodipeptides made up of 17 proteinogenic amino acids. The identification of several CDPSs having the same specificity led us to determine specificity sequence motifs that, in combination with the phylogenetic distribution of CDPSs, provide a first step toward being able to predict the cyclodipeptides synthesized by newly discovered CDPSs. The determination of the activity of ten more CDPSs with predicted functions constitutes a first experimental validation of this predictive approach.
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Isabelle B
authors.initials: IB
authors.lastname: Jacques
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Moutiez
authors.affiliation: Université Paris-Sud, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8621, Institut de Génétique et Microbiologie, Orsay, France.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Witwinowski
authors.affiliation: Université Paris-Sud, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8621, Institut de Génétique et Microbiologie, Orsay, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Darbon
authors.affiliation: Université Paris-Sud, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8621, Institut de Génétique et Microbiologie, Orsay, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Martel
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Seguin
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Favry
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Thai
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lecoq
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Dubois
authors.affiliation: Université Paris-Sud, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8621, Institut de Génétique et Microbiologie, Orsay, France.
authors.forename: Jean-Luc
authors.identifier: 0000000261297093
authors.initials: JL
authors.lastname: Pernodet
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Gondry
authors.affiliation: Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Belin
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D019295:Computational Biology; D003500:Cyclization; D030541:Databases, Genetic; D004151:Dipeptides / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D015870:Gene Expression; D008969:Molecular Sequence Data; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; D005656:Fungal Proteins; D010456:Peptides, Cyclic; D012346:RNA, Transfer, Amino Acyl; D011994:Recombinant Proteins; D010453:Peptide Synthases