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The effect of the dilution rate on CHO cell physiology and recombinant interferon‐γ production in glucose‐limited chemostat culture
Author(s) -
Hayter Paul M.,
Curling Elisabeth M. A.,
Gould Malcolm L.,
Baines Anthony J.,
Jenkins Nigel,
Salmon Ian,
Strange Philip G.,
Bull Alan T.
Publication year - 1993
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.260420909
Subject(s) - chemostat , biochemistry , biology , chinese hamster ovary cell , glycolysis , metabolism , chemistry , genetics , receptor , bacteria
The physiology of a recombinant Chinese hamster ovary cell line in glucose‐limited chemostat culture was studied over a range of dilution rates ( D = 0.008 to 0.20 h −1 ). The specific growth rate (μ) deviated from D at low dilution rates due to an increased specific death rate. Extrapolation of these data suggested a minimum specific growth rate of 0.011 h −1 (μ max = 0.025 h −1 ) The metabolism at each steady state was characterized by determining the metabolic quotients for glucose, lactate, ammonia, amino acids, and interferon‐γ (IFN‐γ). The specific rate of glucose uptake increased linearly with μ, and the saturation constant for glucose ( K s ) was calculated to be 59.6 μM. There was a linear increase in the rate of lactate production with a higher yield of lactate from glucose at high growth rates. The decline in the rate of production of lactate, alanine, and serine at low growth rate was consistent with the limitation of the glycolytic pathway by glucose. The specific rate of IFN‐γ production increased with μ in a manner indicative of a growth‐related product. Despite changes in the IFN‐γ production rate and cell physiology, the pattern of IFN‐γ glycosylation was similar at all except the lowest growth rates where there was increased production of nonglycosylated IFN‐γ. © 1993 John Wiley & Sons, Inc.