N-glycosylation mechanism in insect cells.

描述(申请人提供)：众所周知，昆虫细胞是杆状病毒表达载体(BEV)的宿主，可以通过真核修饰产生大量重组蛋白。昆虫细胞-Bev系统已被用于生产许多不同的重组蛋白，促进了对其结构、功能和在疾病中的作用的生物医学研究。许多公司正在使用昆虫细胞-Bev系统来生产用于高通量功能筛选的重组蛋白质，并开发疫苗、疗法和诊断试剂。将昆虫细胞用于这些应用的优势包括易于放大，成本较低，以及不存在人类不定性剂。这些重要的研究活动需要深入了解昆虫细胞中蛋白质的生物合成和加工途径。然而，这并不是一个主要的研究主题。这项建议侧重于昆虫细胞蛋白的N-糖基化途径。长期目标是提供对昆虫细胞中这一重要代谢途径的明确和详细的看法，并利用这一知识开发具有更广泛的重组糖蛋白处理能力的新的昆虫蛋白生产系统。 在许多重要的生物医学研究项目中，广泛使用昆虫细胞作为蛋白质生产系统是这项研究的一个强有力的理由。智能地利用昆虫细胞生产重组糖蛋白将需要更好地了解它们的N-糖基化途径。这一理解可以指导创新的代谢工程努力，以生产具有改进的N-糖蛋白处理能力的新的昆虫CEFT-BEV系统。昆虫细胞也占据着一个重要的利基市场，作为糖生物学新兴领域基础研究的模型。昆虫细胞N-糖基化途径的复杂性介于低等和高等真核生物的途径之间。因此，昆虫蛋白糖基化途径的明确差异可以被用作开发未来杀虫剂的特定靶点。这可能导致更好的方法来控制在农业和医学上具有重要意义的昆虫及其有助于传播的疾病，这些疾病将对世界各地的公共卫生产生重大影响。

DESCRIPTION (provided by the applicant): Insect cells are widely known as hosts for baculovirus expression vectors (BEVs), which can produce large amounts of recombinant proteins with eukaryotic modifications. The insect cell-BEV system has been used to produce many different recombinant proteins, facilitating biomedical research on their structures, functions, and roles in disease. Many companies are using the insect cell-BEV system to produce recombinant proteins for high-throughput functional screens and to develop vaccines, therapeutics, and diagnostic reagents. The advantages of using insect cells for these applications include ease of scale-up, lower costs, and the absence of human adventitious agents. These important research activities require a dear understanding of protein biosynthesis and processing pathways in insect cells. However, this has not been a major topic of research. This proposal focuses on the insect cell protein N-glycosylation pathway. The long-term goals are to provide an unequivocal and detailed view of this important metabolic pathway in insect cells and to use this knowledge to develop new insect-based protein production systems with more extensive recombinant glycoprotein processing capabilities. The widespread use of insect cells as protein production systems for many important biomedical research projects is a strong justification for this research. Intelligent use of insect cells for recombinant glycoprotein production will require a better understanding of their N-glycosylation pathway. This understanding can direct innovative metabolic engineering efforts to produce new insect ceft-BEV systems with improved N-glycoprotein processing capabilities. Insect cells also occupy an important niche as models for fundamental research in the emerging field of glycobiology. The insect cell N-glycosylation pathway lies in-between the pathways of lower and higher eukaryotes in complexity. Thus, well-defined differences in insect protein glycosylation pathways could be exploited as specific targets to develop future insecticides. This could lead to better ways to control agriculturally and medically important insects and the diseases they help to spread, which would have a major impact on public health, worldwide.