Betenbaugh Michael J, Tomiya Noboru, Narang Someet, Hsu John Ta, Lee Yuan C
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Curr Opin Struct Biol. 2004 Oct;14(5):601-6. doi: 10.1016/j.sbi.2004.09.001.
Insects, yeasts and plants generate widely different N-glycans, the structures of which differ significantly from those produced by mammals. The processing of the initial Glc2Man9GlcNAc2 oligosaccharide to Man8GlcNAc2 in the endoplasmic reticulum shows significant similarities among these species and with mammals, whereas very different processing events occur in the Golgi compartments. For example, yeasts can add 50 or even more Man residues to Man(8-9)GlcNAc2, whereas insect cells typically remove most or all Man residues to generate paucimannosidic Man(3-1)GlcNAc2N-glycans. Plant cells also remove Man residues to yield Man(4-5)GlcNAc2, with occasional complex GlcNAc or Gal modifications, but often add potentially allergenic beta(1,2)-linked Xyl and, together with insect cells, core alpha(1,3)-linked Fuc residues. However, genomic efforts, such as expression of exogenous glycosyltransferases, have revealed more complex processing capabilities in these hosts that are not usually observed in native cell lines. In addition, metabolic engineering efforts undertaken to modify insect, yeast and plant N-glycan processing pathways have yielded sialylated complex-type N-glycans in insect cells, and galactosylated N-glycans in yeasts and plants, indicating that cell lines can be engineered to produce mammalian-like glycoproteins of potential therapeutic value.
昆虫、酵母和植物产生的N-聚糖差异很大，其结构与哺乳动物产生的N-聚糖有显著不同。在内质网中，将最初的Glc2Man9GlcNAc2寡糖加工成Man8GlcNAc2的过程在这些物种与哺乳动物之间显示出显著的相似性，而在高尔基体中则发生非常不同的加工事件。例如，酵母可以在Man(8-9)GlcNAc2上添加50个甚至更多的甘露糖残基，而昆虫细胞通常会去除大部分或所有甘露糖残基，以生成寡甘露糖型的Man(3-1)GlcNAc2 N-聚糖。植物细胞也会去除甘露糖残基以产生Man(4-5)GlcNAc2，偶尔会有复杂的GlcNAc或Gal修饰，但通常会添加潜在的过敏原性β(1,2)-连接的木糖，并且与昆虫细胞一样，添加核心α(1,3)-连接的岩藻糖残基。然而，基因组学方面的努力，如外源糖基转移酶的表达，揭示了这些宿主中更复杂的加工能力，而这些能力在天然细胞系中通常未被观察到。此外，为修饰昆虫、酵母和植物的N-聚糖加工途径而进行的代谢工程努力，已在昆虫细胞中产生了唾液酸化的复合型N-聚糖，在酵母和植物中产生了半乳糖基化的N-聚糖，这表明可以对细胞系进行工程改造，以生产具有潜在治疗价值的类似哺乳动物的糖蛋白。
