Ngk1 kinase ‐mediated N‐acetylglucosamine metabolism promotes UDP‐GlcNAc biosynthesis in Saccharomyces cerevisiae

We uncovered a novel pathway ofN-acetylglucosamine (GlcNAc) metabolism for uridine diphosphateN-acetylglucosamine (UDP-GlcNAc) biosynthesis via Ngk1 kinase inSaccharomyces cerevisiae. GlcNAc phosphorylation by Ngk1 promotes UDP-GlcNAc synthesis and compensates for the hexosamine pathway, a known pathway for UDP-GlcNAc synthesis. The increased synthesis of UDP-GlcNAc by Ngk1 enhances chitin production. N-acetylglucosamine (GlcNAc) is an important structural component of the cell wall chitin,N-glycans, glycolipids, and GPI-anchors in eukaryotes. GlcNAc kinase phosphorylates GlcNAc into GlcNAc-6-phosphate, a precursor of uridine diphosphateN-acetylglucosamine (UDP-GlcNAc) that serves as a substrate for glycan synthesis. Although GlcNAc kinase is found widely in organisms ranging from microorganisms to mammals, it has never been found in the model yeastSaccharomyces cerevisiae. Here, we demonstrate the presence of GlcNAc metabolism for UDP-GlcNAc biosynthesis inS.  cerevisiae through Ngk1, a GlcNAc kinase we discovered previously. The overexpression or deletion of Ngk1 in the presence of GlcNAc affected the amount of both UDP-GlcNAc and chitin, suggesting that GlcNAc metabolism via Ngk1 promotes UDP-GlcNAc synthesis. Our data suggest that the Ngk1-mediated GlcNAc metabolism compensates for the hexosamine pathway, a known pathway for UDP-GlcNAc synthesis.

Source: FEBS Letters - April 16, 2024 Category: Biochemistry Authors: Ayano Nishikawa, Shuichi Karita, Midori Umekawa Tags: Research Letter Source Type: research