Department of Chemical Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark DE, USA.
Biotechnol J. 2012 Jan;7(1):61-74. doi: 10.1002/biot.201100052. Epub 2011 Nov 21.
Chinese hamster ovary (CHO) cells are the most widely used mammalian cell line for biopharmaceutical production, with a total global market approaching $100 billion per year. In the pharmaceutical industry CHO cells are grown in fed-batch culture, where cellular metabolism is characterized by high glucose and glutamine uptake rates combined with high rates of ammonium and lactate secretion. The metabolism of CHO cells changes dramatically during a fed-batch culture as the cells adapt to a changing environment and transition from exponential growth phase to stationary phase. Thus far, it has been challenging to study metabolic flux dynamics in CHO cell cultures using conventional metabolic flux analysis techniques that were developed for systems at metabolic steady state. In this paper we review progress on flux analysis in CHO cells and techniques for dynamic metabolic flux analysis. Application of these new tools may allow identification of intracellular metabolic bottlenecks at specific stages in CHO cell cultures and eventually lead to novel strategies for improving CHO cell metabolism and optimizing biopharmaceutical process performance.
中国仓鼠卵巢（CHO）细胞是生物制药生产中最广泛使用的哺乳动物细胞系，全球市场规模总计接近每年 1000 亿美元。在制药行业中，CHO 细胞在分批补料培养中生长，其细胞代谢的特点是高葡萄糖和谷氨酰胺摄取率，同时伴随着高铵和乳酸盐分泌率。在分批补料培养过程中，CHO 细胞的代谢会发生剧烈变化，因为细胞适应不断变化的环境，并从指数生长阶段过渡到静止阶段。到目前为止，使用传统的代谢通量分析技术来研究 CHO 细胞培养中的代谢通量动态一直具有挑战性，这些技术是为代谢稳态系统开发的。本文综述了 CHO 细胞中的通量分析进展以及动态代谢通量分析技术。这些新工具的应用可能有助于在 CHO 细胞培养的特定阶段确定细胞内代谢瓶颈，并最终为改善 CHO 细胞代谢和优化生物制药工艺性能提供新策略。
