GLMs

glmS refers to two closely related molecular features in bacteria: the glmS gene encoding glucosamine-6-phosphate synthase and the glmS ribozyme, a metabolite-sensing riboswitch embedded in the same mRNA. The glmS gene is widely distributed among bacteria and encodes the enzyme GlmS, a glutamine amidotransferase that catalyzes the first committed step of UDP-N-acetylglucosamine (UDP-GlcNAc) biosynthesis. The reaction combines fructose-6-phosphate with glutamine to produce glucosamine-6-phosphate and glutamate, providing substrates for subsequent steps that generate UDP-GlcNAc, a precursor for peptidoglycan and other cell-wall components. GlmS typically consists of two domains: an N-terminal glutaminase domain that hydrolyzes glutamine to ammonia, and a C-terminal synthase domain where ammonia is transferred to fructose-6-phosphate.

In many Bacillales and other Gram-positive bacteria, glmS mRNA contains in its 5' untranslated region a self-cleaving ribozyme called the glmS ribozyme. Binding of the metabolite glucosamine-6-phosphate activates the ribozyme, causing self-cleavage at a defined site and triggering degradation of the glmS transcript. This provides a negative feedback mechanism that tunes glmS expression to cellular GlcN-6-P levels. The glmS ribozyme is one of the best-characterized metabolite-sensing ribozymes and has been exploited as a tool for gene knockdown in Gram-positive bacteria and for studying riboswitch biology.

The glmS system illustrates how metabolism can regulate gene expression at the RNA level and at the protein level. Both components are considered potential targets for antibacterial strategies, with the enzyme and riboswitch offering different approaches to disrupt cell-wall biosynthesis.