Metabolic flux analysis during galactose and lactate co-consumption reveals enhanced energy metabolism in continuous CHO cell cultures
Metabolic flux analysis during galactose and lactate co-consumption reveals enhanced energy metabolism in continuous CHO cell cultures
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DOI：
10.1016/j.ces.2019.04.049
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发表时间：
2019-09
影响因子：
4.7
通讯作者：
M. Torres;J. Berrios;Yandi Rigual;Y. Latorre;M. Vergara;A. Dickson;C. Altamirano
中科院分区：
文献类型：
--
作者：
M. Torres;J. Berrios;Yandi Rigual;Y. Latorre;M. Vergara;A. Dickson;C. Altamirano
中国人卵巢（CHO）细胞是生产治疗性重组（r-）蛋白的主要表达系统。对这些治疗剂的需求增加促进了更强大的生产工艺的发展。使用优化的补料/培养基显著改善了CHO细胞在培养中的性能。然而，生物质合成和r-蛋白生产的这种进展往往伴随着乳酸盐积累的增加。在这项研究中，我们提出了一种组合的喂养策略，使用半乳糖和乳酸，以取代CHO细胞培养中的葡萄糖。用半乳糖和乳酸盐替代葡萄糖维持CHO细胞中的细胞生长和r-蛋白生产。这种策略支持更好的平衡和更有效的代谢，通过碳源和氨基酸的总体消耗减少来观察，与每C-mol消耗的ATP产量增加相关。我们的研究结果提供了新的见解CHO细胞代谢在无葡萄糖培养基的基础上半乳糖和乳酸。
Chinese Hamster Ovary (CHO) cells are the main expression system for production of therapeutic recombinant (r-) proteins. The increased demand for these therapeutics has boosted the development of more robust production processes. Use of optimised feed/media has dramatically improved the performance of CHO cells in culture. However, such progress in biomass synthesis and r-protein production often come with an increased accumulation of lactate. In this study, we present a combined feeding strategy that uses galactose and lactate to replace glucose in CHO cell cultures. Replacement of glucose by galactose and lactate sustained cell growth and r-protein production in CHO cells. This strategy supported a better-balanced and more efficient metabolism, observed by an overall decreased consumption of carbon sources and amino acids, associated with an increased ATP production per C-mol consumed. Our results provide new insights of CHO cell metabolism in glucose-free media based on galactose and lactate.