Challenges in O-glycan engineering of plants

• Main Author: Richard eStrasser
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2012-09-01
• Series: Frontiers in Plant Science
• Subjects: Glycosylation; Metabolic Engineering; Molecular Farming; Secretory Pathway; glycoprotein; posttranslational modification
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fpls.2012.00218/full

Plants are attractive alternative expression hosts for the production of recombinant proteins. Many therapeutic proteins are glycosylated with N- and O-glycosylation being the most prevalent forms of protein glycosylation. While N-glycans have already been modified in plants towards the formation of homogenous mammalian-type glycoforms with equal or improved biological function compared to mammalian-cell culture produced glycoproteins little attention has been paid to the modification of O-linked glycans. Recently, the first step of mammalian O-glycan biosynthesis has been accomplished in plants. However, as outlined in this short review there are important issues that have to be addressed in the future. These include: (i) elimination of potentially immunogenic or allergenic carbohydrate epitopes containing arabinosides or arabinogalactans. (ii) A detailed investigation of the interplay between engineered N-glycosylation and O-glycosylation pathways to avoid competition for common metabolites like UDP-GlcNAc and (iii) a deeper understanding of signals and mechanisms for distribution of glycan processing enzymes, which is a prerequisite for complete and homogenous glycosylation of recombinant proteins.