Department of Chemical and Biomolecular Engineering, PMB 351604, Vanderbilt University, Nashville, TN 37235-1604, USA; Department of Molecular Physiology and Biophysics, PMB 351604, Vanderbilt University, Nashville, TN 37235-1604, USA.
Curr Opin Biotechnol. 2013 Dec;24(6):1108-15. doi: 10.1016/j.copbio.2013.04.016. Epub 2013 May 28.
Continuous cell lines (CCLs) engage in 'wasteful' glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phenotype, but instead can shift their metabolism toward increased oxidative metabolism as nutrients become depleted and/or growth rate slows. Progress to understand dynamic flux regulation in CCLs has enabled the development of novel strategies to force cultures into desirable metabolic phenotypes, by combining fed-batch feeding strategies with direct metabolic engineering of host cells.
连续细胞系（CCLs）进行“浪费”的葡萄糖和谷氨酰胺代谢，导致抑制性副产物的积累，主要是乳酸盐和铵盐。用于绘制细胞内碳通量图谱和分析酶表达全局变化的技术的进步，使我们对这些代谢变化背后的分子驱动因素有了更深入的了解。然而，最近的研究表明，CCLs 不一定固着于糖酵解或谷氨酰胺分解表型，而是可以随着营养物质的消耗和/或生长速度的减慢，将代谢转向增加的氧化代谢。深入了解 CCLs 中的动态通量调控，使得通过将分批补料策略与宿主细胞的直接代谢工程相结合，开发出将培养物强制进入所需代谢表型的新策略成为可能。
