Metabolic and Bioprocess Engineering of Production Cell Lines for Recombinant Protein Production (Paperback) (ISBN-13: 9783832531232)

Dissolved carbon dioxide has been identified as an important process parameter affecting cell growth, productivity and product quality (e.g. glycosylation) of recombinant proteins when exceeding critical levels, occurring especially in industrial large-scale cell culture processes due to the increased hydrostatic pressure. As CO₂ can easily pass the cellular membrane and thereby influence intracellular pH, important cellular processes (e.g. cell cycle regulation, enzymes of TCA cycle) are directly influenced by pCO₂ and dependent bicarbonate concentration. Consequently, process control strategies attend to keep pCO₂ within physiological range. In a metabolic engineering approach an antibody producing CHO cell line stably expressing human carbonic anhydrase (hCAII), the enzyme that catalyzes the equilibrium of CO₂ in aqueous solutions, was generated and used to characterize CO₂ effects in simulated CO₂ acid load and high CO₂ levels as they occur in large scale mammalian cell culture. The cell line expressing active hCAII showed more rapid initial re-alkalinization of cytoplasm after induced CO₂ acid load.

Author: Betina Da Silva Ribeiro
ISBN-10: 3832531238
ISBN-13: 9783832531232
Publisher: Logos Verlag Berlin
Language: English
Published: 04/16/2012
Pages: 160
Format: Paperback