From media to mitochondria–rewiring cellular energy metabolism of Chinese hamster ovary cells for the enhanced production of biopharmaceuticals

Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Paul S Kelly, Antonio Alarcon Miguez, Christina Alves, Niall BarronMeeting the metabolic demands of Chinese hamster ovary (CHO) cells has been an area of intense investigation over the last 3 decades as a means to improve these cell factories as producers of high quality recombinant therapeutic proteins. Metabolically, the cultivation of CHO cells is characterised by the rapid consumption of the primary carbon and energy sources, glucose and glutamine, with lactate and ammonia produced as by-products, respectively. In the context of bioprocess-relevant CHO cell phenotypes, glycolytic metabolism predominates during exponential cell growth culminating in lactate production while glucose channelling through the tri-carboxylic acid (TCA) cycle supports high-specific productivity. The genetic diversity inherent among CHO cell lineages (CHO-K1, CHO-S, and CHO-DG44), in addition to clonal isolates, makes media development a complex task which must often be performed on a clone by clone basis. However, designing tailored media formulations and sophisticated feeding regimens based on empirical observation has been one of the main driving forces behind the enhancements seen today in volumetric titres. To add to this complexity, CHO mitochondrial genetics have recently been shown to be heterogeneous resulting in an additional level of genetic pre-programming at the epicentre of cellular e...
Source: Current Opinion in Chemical Engineering - Category: Chemistry Source Type: research