Humanization of yeast to produce complex terminally sialylated glycoproteins

被引：343

作者：

Hamilton, Stephen R.

Davidson, Robert C.

Sethuraman, Natarajan

Nett, Juergen H.

Jiang, Youwei

Rios, Sandra

Bobrowicz, Piotr

Stadheim, Terrance A.

Li, Huijuan

Choi, Byung-Kwon

Hopkins, Daniel

Wischnewski, Harry

Roser, Jessica

Mitchell, Teresa

Strawbridge, Rendall R.

Hoopes, Jack

Wildt, Stefan

Gerngross, Tillman U.

机构：

[1] GlycoFi Inc, Lebanon, NH 03766 USA

[2] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA

[3] Dartmouth Coll, Thayer Sch Engn, Dept Biol Sci, Hanover, NH 03755 USA

[4] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA

来源：

SCIENCE | 2006年 / 313卷 / 5792期

关键词：

D O I：

10.1126/science.1130256

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Yeast is a widely used recombinant protein expression system. We expanded its utility by engineering the yeast Pichia pastoris to secrete human glycoproteins with fully complex terminally sialylated N-glycans. After the knockout of four genes to eliminate yeast-specific glycosylation, we introduced 14 heterologous genes, allowing us to replicate the sequential steps of human glycosylation. The reported cell lines produce complex glycoproteins with greater than 90% terminal sialylation. Finally, to demonstrate the utility of these yeast strains, functional recombinant erythropoietin was produced.

引用

页码：1441 / 1443

页数：3

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