Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran.
Appl Microbiol Biotechnol. 2019 Oct;103(20):8315-8326. doi: 10.1007/s00253-019-10048-1. Epub 2019 Aug 15.
The cell culture medium is an intricate mixture of components which has a tremendous effect on cell growth and recombinant protein production. Regular cell culture medium includes various components, and the decision about which component should be included in the formulation and its optimum amount is an underlying issue in biotechnology industries. Applying conventional techniques to design an optimal medium for the production of a recombinant protein requires meticulous and immense research. Moreover, since the medium formulation for the production of one protein could not be the best choice for another protein, hence, the most suitable media should be determined for each recombinant cell line. Accordingly, medium formulation becomes a laborious, time-consuming, and costly process in biomanufacturing of recombinant protein, and finding alternative strategies for medium development seems to be crucial. In silico modeling is an attractive concept to be adapted for medium formulation due to its high potential to supersede laboratory examinations. By emerging the high-throughput datasets, scientists can disclose the knowledge about the effect of medium components on cell growth and metabolism, and via applying this information through systems biology approach, medium formulation optimization could be accomplished in silico with no need of significant amount of experimentation. This review demonstrates some of the applications of systems biology as a powerful tool for medium development and illustrates the effect of medium optimization with system-level analysis on the production of recombinant proteins in different host cells.
细胞培养基是一种复杂的成分混合物，对细胞生长和重组蛋白生产有巨大影响。常规细胞培养基包含各种成分，而关于哪些成分应该包含在配方中及其最佳含量的决定是生物技术行业的一个基本问题。应用传统技术设计用于生产重组蛋白的最佳培养基需要细致和大量的研究。此外，由于一种蛋白质生产的培养基配方可能不是另一种蛋白质的最佳选择，因此，应该为每个重组细胞系确定最合适的培养基。因此，在重组蛋白的生物制造中，培养基配方是一个费力、耗时和昂贵的过程，寻找替代的培养基开发策略似乎至关重要。由于其具有取代实验室检查的高潜力，基于计算的建模是一种有吸引力的概念，可以应用于培养基配方。通过出现高通量数据集，科学家可以揭示关于培养基成分对细胞生长和代谢的影响的知识，并且通过通过系统生物学方法应用这些信息，可以在不进行大量实验的情况下通过计算来完成培养基配方的优化。本文综述了系统生物学作为培养基开发的有力工具的一些应用，并说明了通过系统水平分析对培养基优化对不同宿主细胞中重组蛋白生产的影响。
