Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
Upstream Process Development, Pfizer Inc., 1 Burtt Road, Andover, MA 01810, USA.
Trends Biotechnol. 2020 Oct;38(10):1113-1127. doi: 10.1016/j.tibtech.2020.02.005. Epub 2020 Apr 2.
Mammalian cells are the main tool for the production of therapeutic proteins, viruses for gene therapy, and cells for cell therapy. In production processes cell metabolism is the main driver that causes changes in the growth environment and affects productivity and product quality. Of all nutrients, glucose has the most prominent impact on bioprocesses. We summarize recent findings on the regulation of glucose and energy metabolism in cultured cells. Local allosteric regulations and post-translational modifications of enzymes in metabolic networks interplay with global signaling and transcriptional regulation. These regulatory networks sustain homeostasis across the cytosolic and mitochondrial compartments. Understanding the regulation of glucose metabolism and metabolic state is crucial for enhancing process productivity and product quality.
哺乳动物细胞是生产治疗性蛋白、基因治疗用病毒和细胞治疗用细胞的主要工具。在生产过程中，细胞代谢是主要的驱动因素，它会引起生长环境的变化，从而影响生产力和产品质量。在所有营养素中，葡萄糖对生物过程的影响最为显著。我们总结了最近关于培养细胞中葡萄糖和能量代谢调控的发现。代谢网络中酶的局部变构调节和翻译后修饰与全局信号转导和转录调控相互作用。这些调控网络维持细胞质和线粒体区室的内稳态。了解葡萄糖代谢和代谢状态的调控对于提高工艺生产力和产品质量至关重要。
