中国仓鼠卵巢细胞
生物过程
新陈代谢
生物化学
细胞培养
细胞生长
代谢组学
谷胱甘肽
氨基酸
代谢途径
细胞代谢
生物
化学
代谢工程
计算生物学
生物信息学
酶
受体
古生物学
遗传学
作者
Sara Pereira,Helene Faustrup Kildegaard,Mikael Rørdam Andersen
标识
DOI:10.1002/biot.201700499
摘要
For over three decades, Chinese hamster ovary (CHO) cells have been the chosen expression platform for the production of therapeutic proteins with complex post-translational modifications. However, the metabolism of these cells is far from perfect and optimized, and requires substantial know how and process optimization and monitoring to perform efficiently. One of the main reasons for this is the production and accumulation of toxic and growth-inhibiting metabolites during culture. Lactate and ammonium are the most known, but many more have been identified. In this review, an overview of metabolites that deplete and accumulate throughout the course of cultivations with toxic and growth inhibitory effects to the cells is presented. Further, an overview of the CHO metabolism with emphasis to metabolic pathways of amino acids, glutathione (GSH), and related compounds which have growth-inhibiting and/or toxic effect on the cells is provided. Additionally, relevant publications which describe the applications of metabolomics as a powerful tool for revealing which reactions occur in the cell under certain conditions are surveyed and growth-inhibiting and toxic metabolites are identified. Also, a number of resources that describe the cellular mechanisms of CHO and are available on-line are presented. Finally, the application of this knowledge for bioprocess and medium development and cell line engineering is discussed.
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