Sanofi R&D, 94400 Vitry-sur-Seine, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, 94800 Villejuif, France.
Cells. 2022 Jun 15;11(12):1929. doi: 10.3390/cells11121929.
As indicated by an ever-increasing number of FDA approvals, biotherapeutics constitute powerful tools for the treatment of various diseases, with monoclonal antibodies (mAbs) accounting for more than 50% of newly approved drugs between 2014 and 2018 (Walsh, 2018). The pharmaceutical industry has made great progress in developing reliable and efficient bioproduction processes to meet the demand for recombinant mAbs. Mammalian cell lines are preferred for the production of functional, complex recombinant proteins including mAbs, with Chinese hamster ovary (CHO) cells being used in most instances. Despite significant advances in cell growth control for biologics manufacturing, cellular responses to environmental changes need to be understood in order to further improve productivity. Metabolomics offers a promising approach for developing suitable strategies to unlock the full potential of cellular production. This review summarizes key findings on catabolism and anabolism for each phase of cell growth (exponential growth, the stationary phase and decline) with a focus on the principal metabolic pathways (glycolysis, the pentose phosphate pathway and the tricarboxylic acid cycle) and the families of biomolecules that impact these circuities (nucleotides, amino acids, lipids and energy-rich metabolites).
越来越多的 FDA 批准表明，生物疗法是治疗各种疾病的有力工具，单克隆抗体 (mAbs) 占 2014 年至 2018 年期间批准新药的 50%以上（Walsh，2018）。制药行业在开发可靠和高效的生物生产工艺方面取得了重大进展，以满足对重组 mAbs 的需求。哺乳动物细胞系是生产功能性、复杂重组蛋白（包括 mAbs）的首选，其中大多数情况下使用中国仓鼠卵巢 (CHO) 细胞。尽管在生物制品制造的细胞生长控制方面取得了重大进展，但仍需要了解细胞对环境变化的反应，以进一步提高生产力。代谢组学为开发合适的策略提供了有希望的方法，可以充分挖掘细胞生产的潜力。本综述总结了细胞生长各个阶段（指数增长、静止期和衰退期）的分解代谢和合成代谢的关键发现，重点介绍了主要代谢途径（糖酵解、戊糖磷酸途径和三羧酸循环）以及影响这些回路的生物分子家族（核苷酸、氨基酸、脂质和高能代谢物）。
