Gerngross Tillman U
Thayer School of Engineering, the Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.
Nat Biotechnol. 2004 Nov;22(11):1409-14. doi: 10.1038/nbt1028.
Yeast and fungal protein expression systems are used for the production of many industrially relevant enzymes, and are widely used by the research community to produce proteins that cannot be actively expressed in Escherichia coli or require glycosylation for proper folding and biological activity. However, for the production of therapeutic glycoproteins intended for use in humans, yeasts have been less useful because of their inability to modify proteins with human glycosylation structures. Yeast glycosylation is of the high-mannose type, which confers a short in vivo half-life to the protein and may render it less efficacious or even immunogenic. Several ways of humanizing yeast-derived glycoproteins have been tried, including enzymatically modifying proteins in vitro and modulating host glycosylation pathways in vivo. Recent advances in the glycoengineering of yeasts and the expression of therapeutic glycoproteins in humanized yeasts have shown significant promise, and are challenging the current dominance of therapeutic protein production based on mammalian cell culture.
酵母和真菌蛋白表达系统用于生产许多与工业相关的酶，并且被研究团体广泛用于生产无法在大肠杆菌中有效表达或需要糖基化才能正确折叠和具备生物活性的蛋白质。然而，对于生产供人类使用的治疗性糖蛋白而言，酵母的作用较小，因为它们无法用人类糖基化结构修饰蛋白质。酵母糖基化属于高甘露糖型，这会使蛋白质在体内的半衰期缩短，并可能使其效力降低甚至具有免疫原性。人们尝试了几种使酵母来源的糖蛋白人源化的方法，包括在体外对蛋白质进行酶促修饰以及在体内调节宿主糖基化途径。酵母糖基工程和在人源化酵母中表达治疗性糖蛋白的最新进展已显示出巨大的前景，并正在挑战目前基于哺乳动物细胞培养的治疗性蛋白质生产的主导地位。
