Appropriate Glycosylation of Recombinant Proteins for Human Use: Implications of Choice of Expression System

• Published in: Molecular biotechnology Vol. 28; no. 3; pp. 241 - 256
• Main Author: Brooks, Susan A.
• Format: Journal Article
• Language: English
• Published: Totowa, NJ Humana Press 01.11.2004; Springer Nature B.V
• Subjects: Biological and medical sciences; Biotechnology; Fundamental and applied biological sciences. Psychology; Glycoproteins; Glycosylation; Human subjects; Humans; Protein Processing, Post-Translational; Proteins; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; Yeasts; Human; Posttranslational modification; Biotechnology; Oligosaccharide; posttranslational modification of proteins; oligosaccharides; Glycosylation; Expression systems; Recombinant protein; Gene expression
• ISSN: 1073-6085; 1073-6085; 1559-0305
• DOI: 10.1385/MB:28:3:241

One of the commonest and least well understood posttranslational modifications of proteins is their glycosylation. Human glycoproteins are glycosylated with a bewilderingly heterogeneous array of complex N- and O-linked glycans, which are the product of the coordinated activity of enzymes resident in the endoplasmic reticulum and Golgi apparatus of the cell. Glycosylation of proteins is highly regulated and changes during differentiation, development, under different physiological--and cell culture--conditions and in disease. The glycosylation of recombinant proteins, especially those destined for potential administration to human subjects, is of critical importance. Glycosylation profoundly affects biological activity, function, clearance from circulation, and crucially, antigenicity. The cells of nonhuman species do not glycosylate their proteins in the same way as human cells do. In many cases, the differences are profound. Overall, the species most distant to humans in evolutionary terms, such as bacteria, yeasts, fungi, insects and plants--the species used most commonly in expression systems--have glycosylation repertoires least like our own. This review gives a brief overview of human N- and O-linked protein glycosylation, summarizes what is known of the glycosylation potential of the cells of nonhuman species, and presents the implications for the biotechnology industry.