**4.4. Regulation of GDH synthesis in other Gram-positives**

The *Streptomyces coelicolor* gene *gdhA*, encoding a NADPH-dependent GDH, is negatively regulated under ammonium limitation by GlnR (Figure 3,E). GlnR is an OmpR-like transcriptional factor, which is the master regulator of nitrogen metabolism in *S. coelicolor*. This response includes activation of *glnA*, *glnII* genes, encoding two glutamine synthetases, and repression of *gdhA*, among others [98]. The GlnR regulon appears to be conserved in *Mycobacterium* and other actinomycetes. The nitrogen signal is transduced by a variation of the enterobacterial Ntr signal transduction system, including the PII protein GlnK and GlnD, which catalyzes adenylylation and deadenylylation of GlnK in response to the nitrogen status. GlnR activity is presumably regulated by phosphorylation, as it displays the conserved phosphorylatable aspartate residue present in many response regulators, but the identity of its sensor kinase is currently unknown [99]. GlnR exerts repression of the *gdhA*  promoter region by binding at a conserved site centered at position -73, but the underlying mechanisms of repression are not yet understood [98]. Interestingly, synthesis of the regulator GlnR is repressed by the response regulator PhoP under phosphate limitation, thus providing a link between phosphorus and nitrogen metabolism in *S. coelicolor* [100].

AmtR is a repressor of the TetR family, which acts as the global nitrogen regulator in the industrially relevant *Corynebacterium glutamicum* [Burkowsky, 2003]. Because of the high basal intracellular concentrations of glutamate and glutamine (up to 200 mM and up to 50 mM, respectively), *C. glutamicum* does not use these amino acid pools to sense nitrogen availability. Instead, ammonium is probably used to modulate the activity of the adenylyl transferase GlnD [101]. Adenylylated GlnK interacts with AmtR to release the repressor from its target promoters under nitrogen limitation. AmtR represses the expression of at least 35 genes, including *glnA*, encoding glutamine synthetase, *gltBD*, encoding glutamate synthase and the *amtB-glnK-glnD* operon, encoding a high-affinity ammonium transporter and the signal transduction proteins, GlnK and GlnD. GDH activity is high and relatively constant in different growth conditions [50]. Transcription from the *gdhA*p promoter is repressed 2-fold by AmtR (Figure 3,F) under nitrogen excess and interaction of AmtR with the *gdhA*p promoter region has been detected [102]. Intriguing as it may be, upregulation of GDH under nitrogen limitation does not appear to be physiologically relevant, as sufficient activity is present under the high ammonium concentration conditions in which GDH contributes to ammonium assimilation. Other transcription factors (FarR, WhiH and OxyR) have been documented to bind the *gdhA*p promoter region, but the relevance of these interactions is so far unknown [102].
