Shi Xianzong, Jarvis Donald L
Department of Molecular Biology, University of Wyoming, 1000 E. University Avenue, Laramie, WY 82071, USA.
Curr Drug Targets. 2007 Oct;8(10):1116-25. doi: 10.2174/138945007782151360.
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 N-glycosylation 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.
杆状病毒-昆虫细胞系统的主要优势之一在于它是一种真核系统,能够进行翻译后修饰,比如蛋白质N-糖基化。然而,这是一种极为简化的观点,反映出对昆虫糖生物学的理解不足。一般来说,昆虫蛋白质糖基化途径远比高等真核生物的相应途径简单。矛盾的是,越来越明显的是,各种昆虫以受限的方式编码并能够表达更为复杂的蛋白质糖基化功能。因此,在过去25年里,关于昆虫蛋白质N-糖基化的大量研究中收集到的信息,如今似乎已让人们对杆状病毒-昆虫细胞系统的蛋白质N-糖基化能力有了相当详细、全面且准确的理解。在本章中,我们将讨论从这些研究中得出的昆虫蛋白质N-糖基化模型,以及这如何影响杆状病毒-昆虫细胞系统用于重组糖蛋白生产的应用。我们还将讨论如何将这些模型用作代谢工程研究的基线,以开发具有人源化蛋白质N-糖基化途径的新型杆状病毒-昆虫细胞系统,该系统可用于生产更接近天然的重组N-糖蛋白,用于药物开发和其他生物医学应用。