Emerging methods for the production of homogeneous human glycoproteins

Most circulating human proteins exist as heterogeneously glycosylated variants (glycoforms) of an otherwise homogeneous polypeptide. Though glycan heterogeneity is most likely important to glycoprotein function, the preparation of homogeneous glycoforms is important both for the study of the consequences of glycosylation and for therapeutic purposes. This review details selected approaches to the production of homogeneous human N- and O-linked glycoproteins with human-type glycans. Particular emphasis is placed on recent developments in the engineering of glycosylation pathways within yeast and bacteria for in vivo production, and on the in vitro remodeling of glycoproteins by enzymatic means. The future of this field is very exciting.