Figure 1. Key role of glucosamine-6-phosphate synthase GlmS for bacterial cell envelope synthesis. (A) The hexosamine pathway in Enterobacteriaceae. This pathway generates UDP–GlcNAc from Fru6P and glutamine (Gln) in four sequential reactions catalyzed by enzymes GlmS, GlmM, and GlmU. UDP–GlcNAc is the dedicated precursor for biosynthesis of peptidoglycan and lipopolysaccharides. GlmS catalyzes synthesis of GlcN6P, which is the key reaction. If available, various amino sugars can be taken up and converted to GlcN6P, bypassing the need for GlmS. GlcN6P can also be recycled from degradation of peptidoglycan. Degradation by enzyme NagB allows utilization of GlcN6P as nitrogen and carbon source. (B) Origin and fate of the glmUS transcript in E. coli. Genes glmU and glmS are co-transcribed from two promoters. In the absence of external amino sugars, promoter P1 is activated by transcriptional regulator NagC increasing transcription rates 3-fold. The glmUS co-transcript is processed by RNase E generating monocistronic mRNAs that are usually rapidly degraded. Upon GlcN6P depletion, the glmS mRNA can be stabilized by base-pairing with sRNA GlmZ enhancing GlmS synthesis.