Chinese hamster ovary (CHO) cells in fed-batch cultures produce several
metabolic byproducts derived from amino acid catabolism, some of which
accumulate to growth inhibitory levels. Controlling the accumulation of
these byproducts has been shown to significantly enhance cell
proliferation. Interestingly, some of these byproducts have
physiological roles that go beyond inhibition of cell proliferation. In
this study, we show that, in CHO cell fed-batch cultures, branched chain
amino acid (BCAA) catabolism contributes to the formation of butyrate, a
novel byproduct that is also a well-established specific productivity
enhancer. Further, the other byproducts of BCAA catabolism, isovalerate
and isobutyrate, which accumulate in CHO cell fed-batch cultures also
enhance specific productivity. Additionally, the rate of production of
these BCAA catabolic byproducts was negatively correlated with glucose
uptake and lactate production rates. Limiting glucose supply to suppress
glucose uptake and lactate production, like in case of fed-batch
cultures employing HiPDOG technology, significantly enhances BCAA
catabolic byproduct accumulation resulting in higher specific
productivities.
Scale-down of CHO cell fed-batch cultures