Regulatory insights into the production of UDP-N-acetylglucosamine by lactobacillus casei

Abstract

UDP-N-acetylglucosamine (UDPGlcNAc) is an important sugar nucleotide used as a precursor of cell wall components in bacteria, and as a substrate in the synthesis of oligosaccharides in eukaryotes. In bacteria UDP-GlcNAc is synthesized from the glycolytic intermediate d-fructose-6-phosphate (fructose- 6P) by four successive reactions catalyzed by three enzymes: glucosamine- 6-phosphate synthase (GlmS), phosphoglucosaminemutase (GlmM) and the bi-functional enzyme glucosamine- 1-phosphate acetyltransferase/ N-acetylglucosamine-1-phosphate uridyltransferase (GlmU). We have previously reported a metabolic engineering strategy in Lactobacillus casei directed to increase the intracellular levels of UDPGlcNAc by homologous overexpression of the genes glmS, glmM and glmU. One of the most remarkable features regarding the production of UDP-GlcNAc in L. casei was to find multiple regulation points on its biosynthetic pathway: (1) regulation by the NagB enzyme, (2) glmS RNA specific degradation through the possible participation of a glmS riboswitch mechanism, (3) regulation of the GlmU activity probably by end product inhibition and (4) transcription of glmU. © 2012 Landes Bioscience.