Culture Process Development, Pfizer, Inc., 1 Burtt Road, Andover, MA 01810, USA.
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
Trends Biotechnol. 2016 Aug;34(8):638-651. doi: 10.1016/j.tibtech.2016.04.012. Epub 2016 Jun 2.
Cultured mammalian cells are the main workhorses for producing biologics. The performance of these cell culture processes, in terms of both productivity and product quality attributes, is significantly influenced by cellular metabolism. Glucose is the major carbon source for cellular biosynthesis and energy generation. We summarize here recent advances in our understanding of the regulation of glucose metabolism in cultured cells. The versatility of cells to sustain homeostatic states under widely varying environments is made possible by allosteric regulation of the metabolic network, interplay between the signaling pathways, and transcription factors. Understanding the regulation of metabolism holds the key to altering the metabolic regulatory circuit and implementing direct metabolic control over cell culture processes.
培养的哺乳动物细胞是生产生物制剂的主要工作载体。这些细胞培养过程的性能,无论是在生产力还是产品质量属性方面,都受到细胞代谢的显著影响。葡萄糖是细胞生物合成和能量产生的主要碳源。在这里,我们总结了对培养细胞中葡萄糖代谢调节的最新认识。细胞通过代谢网络的变构调节、信号通路之间的相互作用以及转录因子之间的相互作用,能够在广泛变化的环境中维持稳态,这种多功能性成为可能。理解代谢的调节是改变代谢调节回路并对细胞培养过程实施直接代谢控制的关键。