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Production of Butyrate and Branched Chain Amino Acid Catabolic Byproducts by CHO Cells in Fed-batch Culture Enhances their Specific Productivity
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  • Cameron Harrington,
  • Taylor Kalomeris,
  • Michaela Jacobs,
  • Gregory Hiller,
  • Bhanu Chandra Mulukutla
Cameron Harrington
Pfizer Andover
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Taylor Kalomeris
Pfizer
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Michaela Jacobs
Pfizer
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Gregory Hiller
Pfizer, Inc.
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Bhanu Chandra Mulukutla
Pfizer
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Abstract

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.

Peer review status:IN REVISION

02 Feb 2021Submitted to Biotechnology and Bioengineering
03 Feb 2021Assigned to Editor
03 Feb 2021Submission Checks Completed
11 Feb 2021Reviewer(s) Assigned
14 Mar 2021Review(s) Completed, Editorial Evaluation Pending
14 Mar 2021Editorial Decision: Revise Major