Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures

  1. Get@NRC: Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures (Opens in a new window)
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Journal titleJournal of Biotechnology
Pages122131; # of pages: 10
SubjectAntibodies; Batch cell culture; Cell culture; Cells; Clone cells; Cloning; Cytology; Mammals; Metabolic engineering; Metabolism; Monoclonal antibodies; Cell concentrations; CHO cell; Exponential growth phase; Fed batches; Lactate metabolisms; Mammalian cell lines; Pyruvate carboxylase; Volumetric productivity; Cell engineering; glucose; lactic acid; monoclonal antibody; pyruvate carboxylase; animal cell; bioreactor; cell density; CHO cell line; clone; glycosylation; metabolic engineering; metabolism; nonhuman; nutrient; protein expression; volumetry
AbstractRecombinant yeast pyruvate carboxylase (PYC2) expression was previously shown to be an effective metabolic engineering strategy for reducing lactate formation in a number of relevant mammalian cell lines, but, in the case of CHO cells, did not consistently lead to significant improvement in terms of cell growth, product titer and energy metabolism efficiency. In the present study, we report on the establishment of a PYC2-expressing CHO cell line producing a monoclonal antibody and displaying a significantly altered lactate metabolism compared to its parental line. All clones exhibiting strong PYC2 expression were shown to experience a significant and systematic metabolic shift toward lactate consumption, as well as a prolonged exponential growth phase leading to an increased maximum cell concentration and volumetric product titer. Of salient interest, PYC2-expressing CHO cells were shown to maintain a highly efficient metabolism in fed-batch cultures, even when exposed to high glucose levels, thereby alleviating the need of controlling nutrient at low levels and the potential negative impact of such strategy on product glycosylation. In bioreactor operated in fed-batch mode, the higher maximum cell density achieved with the PYC2 clone led to a net gain (20%) in final volumetric productivity.
Publication date
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics
Peer reviewedYes
NPARC number21277436
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Record identifier661e4ed5-bc72-4307-b2bd-5ab3292d180e
Record created2016-03-09
Record modified2016-05-09
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