中国生物工程杂志

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.