毕赤酵母N-糖基化改造的研究进展

Advances in the asparagines-linked glycosylation in Pichia pastoris

毕赤酵母表达系统具有诸多优点,广泛用于生产重组蛋白。由于其糖基化途径与人不同,表达的糖蛋白为高甘露糖型,改变了糖蛋白的结构,影响其特性和功能,且具有免疫原性,限制了以毕赤酵母为表达系统大量生产重组蛋白的应用。在过去的20多年里,很多研究集中在毕赤酵母N-糖基化人源化改造研究上,希望产生类人的糖链结构,但进展缓慢。近期,毕赤酵母N-糖基化改造研究已经取得了重大进展,产生了类人的末端为唾液酸的糖链结构,为应用毕赤酵母表达系统大量生产重组蛋白铺平了道路。现对毕赤酵母N-糖基化的研究进展进行简述。

With many advantages,Pichia pastoris is widely used to produce recombinant proteins.Due to the differences in N-glycosylation pathway between Pichia pastoris and human,the structure of high-mannose glycan of Pichia pastoris was changed,the characterization and function of the glycoproteins,or even immunogenic were affected.The application of Pichia pastoris to produce glycoproteins was limited.In the past two decades,many researches focused on the modification of N-glycosylation to obtain human-like glycoproteins,yet got limited success.Rencently,great advancements have been made to produce humanized sialylated gycoproteins,which paved the way to use Pichia pastoris as host to produce recombinant proteins.This review summarizes the relevant researches.