Glutamate metabolism in Bacillus subtilis: control of glutamate biosynthesis and evolutionary potential of an alternative route for ammonium assimilation

• Applicant: Professor Dr. Fabian M. Commichau
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550048489

Glutamate is the major amino group donor in every living cell. Two routes for de novo synthesis of glutamate have been described as physiologically relevant: (i) the ATP-independent glutamate dehydrogenase (GDH) pathway and (ii), the ATP-dependent glutamine synthetase (GS)/glutamate synthase (GOGAT) cycle. The Gram-positive model bacterium Bacillus subtilis only uses the GS/GOGAT cycle for glutamate biosynthesis. The GDHs GudB and RocG are strictly devoted to glutamate degradation in vivo. Given the great importance of glutamate for the basic metabolism of the cell, the genes encoding the key components of glutamate metabolism are precisely regulated. During growth of B. subtilis with glucose and ammonium as carbon and nitrogen sources, respectively, the DNA-binding protein GltC activates transcription of the gltAB GOGAT genes to meet the cellular demand for glutamate. At elevated cellular glutamate concentrations, the GDHs bind to GltC and prevent synthesis of the GOGAT. Even though important aspects of glutamate metabolism have been investigated in B. subtilis, it is currently unknown how the catabolically active GDHs control the DNA-binding activity of GltC. By pursuing genetic, biochemical, and structural studies, we aim to uncover how the GDHs convert the transcriptional activator GltC into a repressor of the gltAB genes. Furthermore, we would like to investigate whether an alternative pathway for de novo synthesis of glutamate needs to be regulated in B. subtilis to completely replace the native GS/GOGAT cycle.

• DFG Programme: Research Grants