Biosynthesis and Degradation of Glycans


In the morning of June 20, the session of Biosynthesis and Degradation of Glycans was successfully conducted at the Triumphant Hall of the Seaview Garden Hotel. Prof. Hisashi Narimatsu and Prof. Robert Haltiwanger chaired this part of the thematic session. In the session, Prof. Tamao Endo, Prof. Tadashi Suzuki, Prof. Yang Mao and Prof. Yicheng Wang made wonderful presentations. The overview of this session is as follows:

Prof. Tamao Endo

Professor Tamao Endo (Tokyo Metropolitan Institute of Gerontology, Japan) made a presentation about the Ribitol-phosphate, a new glycan unit in mammalian O-mannosyl glycan. They found fukutin and FKRP were sequentially acting ribitol-phosphate transferases using CDP-ribitol that was synthesized by ISPD. Fukutin forms a complex with POMGnT1, and the POMGnT1-fukutin complex is important to form a platform that requires further glycosylation of the GlcA-Xyl repeat by LARGE. In the presentation, he mainly discussed regulatory mechanism of O-mannosyl glycan biosynthesis of α-DG and their relationship to dystroglycanopathies.

Prof. Tadashi Suzuki

Professor Tadashi Suzuki (RIKEN, Japan) introduced the NGLY1. In the previous study, they analyzed Ngly1-deficient mice and found that they were embryonic lethal in C57BL/6 (B6) background.The additional deletion of Engase, encoding another cytosolic deglycosylating enzyme called ENGase, resulted in the partial rescue of the lethality of the Ngly1-deficient mice. The ERAD dysregulation in Ngly1-KO cells were restored by the additional KO of Engase gene. Their studies reveal that the ENGase represents one of the potential therapeutic targets for this genetic disorder, suggesting the potentiality of therapeutics for NGLY1-deficiency.

Prof. Yang Mao

Professor Yang Mao (Sun Yat-Sen University, China) introduced the deconstruction of the biosynthetic  pathways of  glycosaminoglycans  in  CHO by precise gene editing.They presented an effort to completely  deconstruct the GAG biosynthesis using the CRISPR/Cas9. By precisely knocking out the GAG biosynthetic enzymes individually or in combination in CHO cells, they can gauge the contribution of each  isoenzyme to the capacity of CHO to make GAGs and uncovers potential enzyme-enzyme interactions in the GAG biosynthesis. Their study provides a new perspective on the biosynthesis of  GAGs in  mammalian  cells  and  offers  new  hope  on  dissecting  the  long  hypothesized  “GAGosome”.

Prof. Yicheng Wang

Professor Yicheng Wang (Osaka University, Japan) introduced their study about Beta-1,3-galactosyltransferase.They found beta-1,3-galactosyltransferase 4 transfers Gal not only to ganglioside substrates, but also to GPI-GalNAc. The current results suggest a requirement of LacCer for efficient GPI galactosylation. Therefore, pathways for GPI-AP biosynthesis and ganglioside biosynthesis cross at the steps mediated by beta-1,3-galactosyltransferase 4.