Comparative genomics of pyridoxal 5′-phosphate-dependent transcription factor regulons in Bacteria

Abstract

The MocR-subfamily transcription factors (MocR-TFs) characterized by the GntR-family DNA-binding domain and aminotransferase-like sensory domain are broadly distributed among certain lineages of Bacteria. Characterized MocR-TFs bind pyridoxal 5′-phosphate (PLP) and control transcription of genes involved in PLP, gamma aminobutyric acid (GABA) and taurine metabolism via binding specific DNA operator sites. To identify putative target genes and DNA binding motifs of MocR-TFs, we performed comparative genomics analysis of over 250 bacterial genomes. The reconstructed regulons for 825 MocR-TFs comprise structural genes from over 200 protein families involved in diverse biological processes. Using the genome context and metabolic subsystem analysis we tentatively assigned functional roles for 38 out of 86 orthologous groups of studied regulators. Most of these MocR-TF regulons are involved in PLP metabolism, as well as utilization of GABA, taurine and ectoine. The remaining studied MocR-TF regulators presumably control genes encoding enzymes involved in reduction/oxidation processes, various transporters and PLP-dependent enzymes, for example aminotransferases. Predicted DNA binding motifs of MocR-TFs are generally similar in each orthologous group and are characterized by two to four repeated sequences. Identified motifs were classified according to their structures. Motifs with direct and/or inverted repeat symmetry constitute the majority of inferred DNA motifs, suggesting preferable TF dimerization in head-to-tail or head-to-head configuration. The obtained genomic collection of in silico reconstructed MocR-TF motifs and regulons in Bacteria provides a basis for future experimental characterization of molecular mechanisms for various regulators in this family.

Transcriptional regulation of ectoine catabolism in response to multiple metabolic and environmental cues

“…Using comparative genomics and metabolic reconstruction, Suvorova and Rodionov () recently analysed the distribution of MocR/GabR‐type regulators in a non‐redundant set of 390 microbial genomes representing 43 diverse lineages of Bacteria . They predicted the putative operator binding sites of various sub‐groups of this family of transcriptional regulators through bioinformatics.…”

“…We searched the 433 bp DNA‐fragment (Fig. A) carried by the EnuR‐responsive uehA‐lacZ operon fusion plasmid pBAS21 for the presence of DNA sequences resembling the EutR consensus sequence proposed by Suvorova and Rodionov (). We found two possible operator binding sites for EnuR in the 97 bp intergenic region between the 3'‐end of the enuR gene and the 5'‐end of uehA (Fig.…”

Evidence that COG0325 proteins are involved in PLP homeostasis

“…S2). Indeed, yggS genes were found associated with pdxK, glyA and B6 transporter genes in operons predicted to be under the control of various PdxR-type PLP-responsive transcription regulators (Jochmann et al, 2011;Suvurova & Rodionov, 2016;Tramonti et al, 2015) (Figs 2b and S2). Finally, genes encoding essential ATP-dependent enzymes (with essential lysines) were found to cluster strongly with yggS (Table 1).…”

Salmonella typhimurium PtsJ is a novel MocR‐like transcriptional repressor involved in regulating the vitamin B6 salvage pathway

“…Our study on PtsJ adds to a recent series of interesting investigations demonstrating that a variety of functional and structural features are present in MocRs and that distinct subgroups exist in this family of transcriptional regulators, having different targets and action mechanisms .…”

“…It was recently shown by our research group that predicted MocR linkers vary in length, going from a minimum of about 8–9 residues to a maximum, in a few cases, of about 150 residues . This striking heterogeneity may reflect the functional diversification of MocR regulators, the variety of the controlled genes, and the different mechanisms of DNA recognition . In addition, the TFBSs of the so far characterised MocRs show the lack of any conservation in sequence and position with respect to the target genes.…”