title: Tracking dipeptides at work-uptake and intracellular fate in CHO culture.
abstract: Market demands for monoclonal antibodies (mAbs) are steadily increasing worldwide. As a result, production processes using Chinese hamster ovary cells (CHO) are in the focus of ongoing intensification studies for maximizing cell-specific and volumetric productivities. This includes the optimization of animal-derived component free (ADCF) cultivation media as part of good cell culture practice. Dipeptides are known to improve CHO culture performance. However, little or even conflicting assumptions exist about their putative import and functionality inside the cells. A set of well-known performance boosters and new dipeptide prospects was evaluated. The present study revealed that dipeptides are indeed imported in the cells, where they are decomposed to the amino acids building blocks. Subsequently, they are metabolized or, unexpectedly, secreted to the medium. Monoclonal antibody production boosting additives like L-alanine-L-glutamine (AQ) or glycyl-L-glutamine (GQ) can be assigned to fast or slow dipeptide uptake, respectively, thus pinpointing to the need to study dipeptide kinetics and to adjust their feeding individually for optimizing mAb production.
authors.affiliation: Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.|CEQIATEC, Costa Rica Institute of Technology (TEC), Cartago, Costa Rica.
authors.forename: Andres
authors.initials: A
authors.lastname: Sánchez-Kopper
authors.affiliation: Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Becker
authors.affiliation: Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pfizenmaier
authors.affiliation: Evonik Nutrition & Care GmbH, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kessler
authors.affiliation: Evonik Nutrition & Care GmbH, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Karau
authors.affiliation: Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. ralf.takors@ibvt.uni-stuttgart.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Takors
keywords: CHO cells; Culture medium; Dipeptide uptake; mAb production