Lactate Control Enhances Growth Advantage in Fed-batch Cultures of
Metabolically Engineered CHO Cells with Reduced Novel Growth-inhibitory
Compound Formation
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.