酵母表达人源化糖蛋白研究进展

与人体天然复杂型糖蛋白相比，使用酵母生产的药用蛋白带有高甘露糖型N-糖链。这一差异在临床应用中产生了许多不良影响。目前，可以通过消除酵母特有的内源糖基化反应，引入哺乳动物细胞中的一系列糖基转移酶及转运蛋白对酵母糖基化路径进行改造，从而使其表达出人源化的复杂型N-聚糖。本文介绍了酵母N-糖基化特点、糖基化不均一性，综述了近年来利用基因工程改造酵母N-糖基化路径获得特定的人源N-连接糖蛋白以及使用内切糖苷酶生产人源糖蛋白的研究进展，并且对存在的问题及今后的发展前景进行了讨论。

Advances in the Expression of Humanized Glycoprotein in Yeast

Compared with complex glycoproteins in humans, therapeutic proteins produced in yeast expression systems typically carry high-mannose sugar chains which can lead to rapid clearance, enhanced immunogenicity and poor pharmacokinetic behaviour in clinical application. After the recreation of the N-glycosylation pathways by eliminating endogenous glycosylation reactions, introducing mammalian glycosyltransferases and expressing some sugar transporters, human-like complex glycoproteins with terminal sialic acids could be produced. This review summarizes yeast N-linked glycosylation processes, the heterogeneity of glycosylation, the genetic engineering of yeast glycosylation pathways to produce fully humanized glycoproteins and the application of endo-β-N-acetylglucosaminidase for in vitro synthesis of complex glycoproteins in recent years. Moreover, existing problems and future development directions are discussed.