Glucosamine metabolism and new glucosamine-1P fate by alternative enzyme activities in Rhodococcus

ASENCION DIEZ MD; IGLESIAS AA; CEREIJO AE

San Martin, Buenos Aires

Simposio; 3rd Argentinian Symposium on Glycobiology-GlycoAr; 2019

Theamino sugar glucosamine (GlcN) is an essential component of glycosaminoglycansand glycoproteins. It is one of the most prevalent sugars in the biosphere, amajor module in bacterial cell envelope and constitutes a glycosidic unit in manyantibiotics. Consistent with this importance, pathways for amino sugar metabolismare conserved in bacteria, where GlcN-6P is a key regulator connecting thepathways to glycolysis or triggering antibiotic synthesis in Actinobacteria.Instead, GlcN-1P isdescribed as a mere intermediary in the pathway from GlcN-6P to UDP-N-acetyl-GlcN. We show herethat the GlgAC enzymes from the glycogen synthesis pathway in Rhodococcus spp. efficiently use GlcN-1P.The latter is a substrate of ADP-glucose pyrophosphorylase, being this activitysensitive to the enzyme effectors (GlcN-6P amongst them). The actinobacterialglycogen synthase uses ADP-Glc and glucose-1P to synthesize maltose-1P and wefound that GlcN-1P is also a substrate for this reaction in the rhodococcal enzyme.In addition, we describe a new pyrophosphorylase able to specifically use GlcN-1Pand UTP. Taking together, results suggest a fate for GlcN-1P different than justan intermediary leading to N-acetyl-GlcN.We propose a revision of GlcN metabolism in organisms of high biotechnologicalrelevance. Also, we show an important source to study the evolution ofcarbohydrate related enzymes and a putative new tool for precision synthesis ofnovel sugar compounds.