Variants of the LysR-Type Regulator GltC With Altered Activator and Repressor Function

The Gram-positive soil bacterium relies on the glutamine synthetase and the glutamate synthase for glutamate biosynthesis from ammonium and 2-oxoglutarate. During growth with the carbon source glucose, the LysR-type transcriptional regulator GltC activates the expression of the glutamate synthase genes. With excess of intracellular glutamate, the genes are not transcribed because the glutamate-degrading glutamate dehydrogenases (GDHs) inhibit GltC. Previous studies revealed that 2-oxoglutarate and glutamate stimulate the activator and repressor function, respectively, of GltC. Here, we have isolated GltC variants with enhanced activator or repressor function. The majority of the GltC variants with enhanced activator function differentially responded to the GDHs and to glutamate. The GltC variants with enhanced repressor function were still capable of activating the promoter in the absence of a GDH. Using promoter variants ( ) that are active independent of GltC, we show that the wild type GltC and the GltC variants with enhanced repressor function inactivate promoters in the presence of the native GDHs. These findings suggest that GltC may also act as a repressor of the genes We discuss a model combining previous models that were derived from and experiments.