An increasing number of optimization strategies are being reported to improve mammalian cells culture and associated protein production. However, the universal success of these approaches remains mixed. One reason is that we lack a holistic integrated understanding of the mechanisms underlying the metabolic and physiological phenomena leading to high-production phenotypes. However the systems biology context will allow us to integrate such understanding as we leverage resources from sequencing projects to reconstruct cell-line specific genome scale models (GeMs). GeMs offer the possibility of describing and quantifying all the metabolic reactions within a defined organism under very specific culture conditions. While these complex models are very useful to help us understand cellular metabolism, their size can limit their use with several algorithms and optimization strategies. Further efforts to improve mammalian-based production processes are anticipated to require a better understanding of the cellular basis for high productivity, and therefore, there is a need to define the most basic and essential pathways leading to the acquisition of “super-producer” cell phenotype. Thus, we have developed an unbiased approach to extract a core metabolic model from the GeM of CHO cells. This model contains a reduced set of dominant metabolic pathways that fulfills the main metabolic capabilities required for growth and protein production. This implies that any changes in desired cellular phenotype would involve changes in these key metabolic pathways. This simplified description of cell metabolism will allow researchers to elucidate and quantify the interconnection of metabolism to the other cellular processes underlying protein production.

Development of a core model of CHO cell metabolism

253rd National Meeting (2017)

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