The synthesis of glutamine synthetase (GS), a key enzyme in ammonium (NH4+) assimilation, is regulated by nitrogen availability in several Streptomyces strains. In addition, the enzymatic activity of the GS enzyme is post-translationally regulated by adenylylation. Nitrogen regulation of GS synthesis is mediated at the transcriptional level in S. coelicolor, and transcription of the GS structural gene (glnA) requires a positive regulatory protein, GlnR. The amino acid sequence of the GlnR protein is similar to that of the Escherichia coli positive regulatory proteins, OmpR and PhoB, which belong to the family of bacterial two-component regulatory systems. DNA encoding a GSII-like enzyme has been cloned from S. viridochromogenes and S. hygroscopicus, but the role of this GS isoenzyme in NH4+ assimilation in Streptomyces is unclear.