Microbiology and Kluyver Centre for Genomics of Industrial Fermentations, Utrecht University, Utrecht, The Netherlands.
Glycobiology. 2013 Feb;23(2):147-54. doi: 10.1093/glycob/cws135. Epub 2012 Sep 20.
Alg3 of Saccharomyces cerevisiae catalyzes the mannosyl transfer from Man-P-Dol to Man(5)GlcNAc(2)-PP-Dol resulting in the formation of Man(6)GlcNAc(2)-PP-Dol, which is then further processed to the final precursor oligosaccharide Glc(3)Man(9)GlcNAc(2) for N-glycosylation of proteins. Here, we identified the alg3 gene of the mushroom-forming fungus Schizophyllum commune by homology search. Its function was confirmed by the complementation of the Δalg3 strain of S. cerevisiae. Inactivation of alg3 in S. commune resulted in the production of predominantly Man(3)GlcNAc(2) protein-linked N-glycans. No impact on growth nor a developmental phenotype due to the deletion was observed. This provides a first step toward engineering of a homogeneous, humanized N-glycosylation pattern for the production of therapeutic glycoproteins in mushrooms.
酿酒酵母的 Alg3 酶催化甘露糖从 Man-P-Dol 转移到 Man(5)GlcNAc(2)-PP-Dol,从而形成 Man(6)GlcNAc(2)-PP-Dol,然后进一步加工成最终的前体寡糖 Glc(3)Man(9)GlcNAc(2),用于蛋白质的 N-糖基化。在这里,我们通过同源搜索鉴定了蘑菇形成真菌裂褶菌的 alg3 基因。通过对酿酒酵母 Δalg3 菌株的互补,证实了其功能。alg3 在裂褶菌中的失活导致主要产生 Man(3)GlcNAc(2)蛋白连接的 N-聚糖。由于缺失,对生长或发育表型没有影响。这为在蘑菇中生产治疗性糖蛋白的同质、人源化 N-糖基化模式的工程化提供了第一步。