title: Comparative genome analysis of central nitrogen metabolism and its control by GlnR in the class Bacilli.
abstract: BACKGROUND
  The assimilation of nitrogen in bacteria is achieved through only a few metabolic conversions between alpha-ketoglutarate, glutamate and glutamine. The enzymes that catalyze these conversions are glutamine synthetase, glutaminase, glutamate dehydrogenase and glutamine alpha-ketoglutarate aminotransferase. In low-GC Gram-positive bacteria the transcriptional control over the levels of the related enzymes is mediated by four regulators: GlnR, TnrA, GltC and CodY. We have analyzed the genomes of all species belonging to the taxonomic families Bacillaceae, Listeriaceae, Staphylococcaceae, Lactobacillaceae, Leuconostocaceae and Streptococcaceae to determine the diversity in central nitrogen metabolism and reconstructed the regulation by GlnR.
  
  
  RESULTS
  Although we observed a substantial difference in the extent of central nitrogen metabolism in the various species, the basic GlnR regulon was remarkably constant and appeared not affected by the presence or absence of the other three main regulators. We found a conserved regulatory association of GlnR with glutamine synthetase (glnRA operon), and the transport of ammonium (amtB-glnK) and glutamine/glutamate (i.e. via glnQHMP, glnPHQ, gltT, alsT). In addition less-conserved associations were found with, for instance, glutamate dehydrogenase in Streptococcaceae, purine catabolism and the reduction of nitrite in Bacillaceae, and aspartate/asparagine deamination in Lactobacillaceae.
  
  
  CONCLUSIONS
  Our analyses imply GlnR-mediated regulation in constraining the import of ammonia/amino-containing compounds and the production of intracellular ammonia under conditions of high nitrogen availability. Such a role fits with the intrinsic need for tight control of ammonia levels to limit futile cycling.
authors.affiliation: Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Groot Kormelink
authors.forename: Eric
authors.initials: E
authors.lastname: Koenders
authors.forename: Yanick
authors.initials: Y
authors.lastname: Hagemeijer
authors.forename: Lex
authors.initials: L
authors.lastname: Overmars
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Siezen
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.forename: Christof
authors.initials: C
authors.lastname: Francke
mesh_terms: D000595:Amino Acid Sequence; D000641:Ammonia / Q000378:metabolism; D001406:Bacillaceae / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D007777:Lactobacillaceae / Q000201:enzymology / Q000235:genetics; D056584:Leuconostocaceae / Q000201:enzymology / Q000235:genetics; D008087:Listeria / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D040141:Staphylococcaceae / Q000201:enzymology / Q000235:genetics; D013289:Streptococcaceae / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C101458:ScgR protein, Bacillus subtilis; D000641:Ammonia; D004247:DNA; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen