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Lactate Control Enhances Growth Advantage in Fed-batch Cultures of Metabolically Engineered CHO Cells with Reduced Novel Growth-inhibitory Compound Formation
  • Quentin Bethune,
  • Cameron Harrington,
  • Bhanu Mulukutla
Quentin Bethune
Pfizer Andover
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Cameron Harrington
Pfizer Andover
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Bhanu Mulukutla
Pfizer Andover
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Abstract

CHO cells have been recently shown to produce amino acid catabolism derived byproducts, which accumulate in fed-batch cultures to growth-inhibitory levels. Residual amino acid limitation or genetic engineering strategies have been successfully employed to suppress production of these novel growth inhibitory metabolic byproducts. However, the growth advantage attained due to suppression of these metabolic byproducts in fed-batch cultures is more pronounced when lactate accumulation is also controlled. BCAT1 knock-out (KO) CHO cells, which produce negligible levels of the metabolic byproducts isovalerate, isobutyrate and 2-methylbutyrate, grow to significantly higher peak cell densities in fed-batch cultures with lactate control (HiPDOG) as compared to cultures without lactate control. Henceforth, strategies involving novel metabolic byproduct control should preferably include lactate control to more easily assess the enhanced cell growth and productivities attainable.