Production of complex human glycoproteins in yeast - PubMed

Affiliations

• PMID: 12947202
• DOI: 10.1126/science.1088166

Production of complex human glycoproteins in yeast

Stephen R Hamilton et al. Science. 2003.

Abstract

We report the humanization of the glycosylation pathway in the yeast Pichia pastoris to secrete a human glycoprotein with uniform complex N-glycosylation. The process involved eliminating endogenous yeast glycosylation pathways, while properly localizing five active eukaryotic proteins, including mannosidases I and II, N-acetylglucosaminyl transferases I and II, and uridine 5'-diphosphate (UDP)-N-acetylglucosamine transporter. Targeted localization of the enzymes enabled the generation of a synthetic in vivo glycosylation pathway, which produced the complex human N-glycan N-acetylglucosamine2-mannose3-N-acetylglucosamine2 (GlcNAc2Man3GlcNAc2). The ability to generate human glycoproteins with homogeneous N-glycan structures in a fungal host is a step toward producing therapeutic glycoproteins and could become a tool for elucidating the structure-function relation of glycoproteins.

Comment in

• Biotechnology. Yeast engineered to produce sugared human proteins.

  Service RF. Service RF. Science. 2003 Aug 29;301(5637):1171. doi: 10.1126/science.301.5637.1171. Science. 2003. PMID: 12947173 No abstract available.

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