Protein Glycosylation

Abstract

More than half of the proteins synthesized by humans are glycosylated. That is, the proteins have one or more N‐ or O‐ linked glycan chains attached to them. Proteins are naturally synthesized in a range of glycoforms, and their glycosylation profile influences their activity, stability, immunogenicity, serum half life, and other biological properties. While the general mechanisms of human protein glycosylation are well established, what influences the fine control of glycosylation patterns is not well understood. Furthermore, the cells of organisms other than humans glycosylate their proteins differently. This is of interest to the biotechnology industry, which commonly uses nonhuman cells for protein expression. Proteins expressed in cells of nonhuman species are glycosylated differently to how they would be by human cells and this is of particular relevance to expression of glycoproteins destined for potential administration to humans. Inappropriate glycosylation profiles result in altered and undesirable pharmokinetic properties. In this chapter, the mechanisms of human protein glycosylation are explained. Glycosylation in cells of nonhuman species, including prokaryotes, fungi and yeasts, insects, plants, and mammals other than humans are introduced, with an emphasis on glycosylation differences of importance to the biotechnology industry. Important advances in engineering glycosylation in nonhuman cell expression systems are highlighted.