Zhang Huan-Yu, Fan Zhen-Lin, Wang Tian-Yun
Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, China.
International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang, China.
Front Bioeng Biotechnol. 2021 Dec 2;9:774175. doi: 10.3389/fbioe.2021.774175. eCollection 2021.
As the most widely used mammalian cell line, Chinese hamster ovary (CHO) cells can express various recombinant proteins with a post translational modification pattern similar to that of the proteins from human cells. During industrial production, cells need large amounts of ATP to support growth and protein expression, and since glycometabolism is the main source of ATP for cells, protein production partly depends on the efficiency of glycometabolism. And efficient glycometabolism allows less glucose uptake by cells, reducing production costs, and providing a better mammalian production platform for recombinant protein expression. In the present study, a series of progresses on the comprehensive optimization in CHO cells by glycometabolism strategy were reviewed, including carbohydrate intake, pyruvate metabolism and mitochondrial metabolism. We analyzed the effects of gene regulation in the upstream and downstream of the glucose metabolism pathway on cell's growth and protein expression. And we also pointed out the latest metabolic studies that are potentially applicable on CHO cells. In the end, we elaborated the application of metabolic models in the study of CHO cell metabolism.
作为使用最广泛的哺乳动物细胞系,中国仓鼠卵巢(CHO)细胞能够表达各种重组蛋白,其翻译后修饰模式与人类细胞蛋白相似。在工业生产过程中,细胞需要大量ATP来支持生长和蛋白表达,由于糖代谢是细胞ATP的主要来源,蛋白生产部分取决于糖代谢效率。高效的糖代谢使细胞对葡萄糖的摄取减少,降低了生产成本,并为重组蛋白表达提供了更好的哺乳动物生产平台。在本研究中,综述了通过糖代谢策略对CHO细胞进行全面优化的一系列进展,包括碳水化合物摄取、丙酮酸代谢和线粒体代谢。我们分析了葡萄糖代谢途径上下游的基因调控对细胞生长和蛋白表达的影响。并且我们还指出了可能适用于CHO细胞的最新代谢研究。最后,我们阐述了代谢模型在CHO细胞代谢研究中的应用。