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Perfusion cultures require optimum respiratory ATP supply to maximize cell‐specific and volumetric productivities
Author(s) -
Becker Max,
Junghans Lisa,
Teleki Attila,
Bechmann Jan,
Takors Ralf
Publication year - 2019
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.26926
Subject(s) - adenosine triphosphate , oxidative phosphorylation , cellular respiration , biochemistry , glycolysis , perfusion , atp synthase , respiration , biology , cytosol , metabolism , steady state (chemistry) , nicotinamide adenine dinucleotide , chemistry , nad+ kinase , mitochondrion , medicine , enzyme , botany
Perfusion processes are an emerging alternative to common fed‐batch processes in the growing biopharmaceutical industry. However, the challenge of maintaining high cell‐specific productivities remains. In this study, glucose limitation was applied to two perfusion steady states and compared with a third steady state without any detectable limitation. The metabolic phenotype was enhanced under glucose limitation with a decrease of 30% in glucose uptake and 75% in lactate formation. Cell‐specific productivities were substantially improved by 50%. Remarkably, the productivities showed a strong correlation to respiratory adenosine triphosphate (ATP) supply. As less reduced nicotinamide adenine dinucleotide (NADH) remained in the cytosol, the ATP generation from oxidative phosphorylation was increased by almost 30%. Consequently, the efficiency of carbon metabolism and the resulting respiratory ATP supply was crucial for maintaining the highly productive cellular state. This study highlights that glucose limitation can be used for process intensification in perfusion cultures as ATP generation via respiration is significantly increased, leading to elevated productivities.