title: Identification of a missing link in the evolution of an enzyme into a transcriptional regulator.
abstract: The evolution of transcriptional regulators through the recruitment of DNA-binding domains by enzymes is a widely held notion. However, few experimental approaches have directly addressed this hypothesis. Here we report the reconstruction of a plausible pathway for the evolution of an enzyme into a transcriptional regulator. The BzdR protein is the prototype of a subfamily of prokaryotic transcriptional regulators that controls the expression of genes involved in the anaerobic degradation of benzoate. We have shown that BzdR consists of an N-terminal DNA-binding domain connected through a linker to a C-terminal effector-binding domain that shows significant identity to the shikimate kinase (SK). The construction of active synthetic BzdR-like regulators by fusing the DNA-binding domain of BzdR to the Escherichia coli SKI protein strongly supports the notion that an ancestral SK domain could have been involved in the evolutionary origin of BzdR. The loss of the enzymatic activity of the ancestral SK domain was essential for it to evolve as a regulatory domain in the current BzdR protein. This work also supports the view that enzymes precede the emergence of the regulatory systems that may control their expression.
authors.affiliation: Department of Environmental Biology, Centro de Investigaciones Biológicas-CSIC, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Durante-Rodríguez
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Mancheño
authors.forename: Germán
authors.initials: G
authors.lastname: Rivas
authors.forename: Carlos
authors.initials: C
authors.lastname: Alfonso
authors.forename: José Luis
authors.initials: JL
authors.lastname: García
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz
authors.forename: Manuel
authors.initials: M
authors.lastname: Carmona
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D008958:Models, Molecular; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C037817:benzoyl-coenzyme A; D017853:Phosphotransferases (Alcohol Group Acceptor); C022642:shikimate kinase