Protein N-Glycosylation in the Baculovirus-Insect Cell System

One of the major advantages of the baculovirus-insect cell system is that it is a eukaryotic system that can provide posttranslational modifications, such as protein N-glycosylation. However, this is a vastly oversimplified view, which reflects a poor understanding of insect glycobiology. In general, insect protein glycosylation pathways are far simpler than the corresponding pathways of higher eukaryotes. Paradoxically, it is increasingly clear that various insects encode and can express more elaborate protein glycosylation functions in restricted fashion. Thus, the information gathered in a wide variety of studies on insect protein N-glycosylation during the past 25 years has provided what now appears to be a reasonably detailed, comprehensive, and accurate understanding of the protein Nglycosylation capabilities of the baculovirus-insect cell system. In this chapter, we discuss the models of insect protein N-glycosylation that have emerged from these studies and how this impacts the use of baculovirus-insect cell systems for recombinant glycoprotein production. We also discuss the use of these models as baselines for metabolic engineering efforts leading to the development of new baculovirus- insect cell systems with humanized protein N-glycosylation pathways, which can be used to produce more authentic recombinant N-glycoproteins for drug development and other biomedical applications.