Systems biology approach in the formulation of chemically defined media for recombinant protein overproduction.

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.