Control of glutamate homeostasis in Bacillus subtilis: a complex interplay between ammonium assimilation, glutamate biosynthesis and degradation.

Glutamate, the major amino group donor in anabolism, is synthesized by the combined action of the glutamine synthetase (GS) and the glutamate synthase (GOGAT) in Bacillus subtilis. The glutamate dehydrogenase (GDH) exclusively degrades glutamate. GS and GDH are both trigger enzymes, active in nitrogen metabolism and in controlling gene expression. Feedback-inhibited GS (FBI-GS) controls DNA-binding activities of two transcription factors, the repressor GlnR and TnrA, the global regulator of nitrogen metabolism. FBI-GS binds to and activates GlnR. This protein complex inhibits GS formation and thus glutamine synthesis. Moreover, FBI-GS inhibits DNA-binding activity of TnrA. Glutamate biosynthesis, the reaction linking carbon with nitrogen metabolism, is controlled by GDH. Together with glutamate GDH inhibits GltC, the transcription factor that activates expression of the GOGAT genes. Thus, GS and GDH control glutamine and glutamate synthesis, respectively, depending on the nitrogen status of the cell. B. subtilis lacking a functional GDH show a severe growth defect. Interestingly, the growth defect is suppressed by the rapid activation of an inactive GDH. Thus, maintenance of glutamate homeostasis is crucial for cellular vitality. This review covers the recent work on the complex control of glutamine and glutamate metabolism in the Gram-positive model organism B. subtilis.