Metabolic responses and pathway changes of mammalian cells under different culture conditions with media supplementations

Abstract

Amino acids and glucose consumption, cell growth and monoclonal antibody (mAb) production in mammalian cell culture are key considerations during upstream process and particularly media optimization. Understanding the interrelations and the relevant cellular physiology will provide insight for setting strategy of robust and effective mAb production. The aim of this study was to further our understanding of nutrient consumption metabolism, since this could have significant impact on enhancing mAb titer, cell proliferation, designing feeding strategies, and development of feed media. The nutrient consumption pattern, mAb concentration, and cell growth were analyzed in three sets of cell cultures with media supplementation of glucose, methionine, threonine, tryptophan, and tyrosine. The amino acids metabolism and its impact on cell growth and mAb production during the batch and fed-batch culture were closely analyzed. It was shown that the phenylalanine, tyrosine and tryptophan biosynthesis pathways were significantly altered under different culture conditions with different media. These changes were more apparent in the fed-batch process in which higher mAb titer was observed due to the metabolic changes than mAb titer in the batch process. The pathway analysis approach was well utilized for evaluating the impact on the relevant pathways involved under different cell culture conditions to improve cell growth and mAb titer. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:793-805, 2018.

The organic loading rate affects organic micropollutants’ cometabolic biotransformation kinetics under heterotrophic conditions in activated sludge

“…One explanation for such behaviour could be that media conditions and especially process conditions, such as operating in batch mode rather than in a continuous manner, could lead to a different intensity in the metabolic responses, in agreement with the results from Park et al (2018). Besides, microorganisms may have followed different enzymatic routes in the batch and reactor experiments to degrade the substrates due to variations in the initial feeding concentrations, in consonance with previous studies…”

Genetic and Epigenetic Variation across Genes Involved in Energy Metabolism and Mitochondria of Chinese Hamster Ovary Cell Lines

“…However, other pathways enriched for “mutated genes” include lipoic acid metabolism, nitrogen metabolism, cysteine and methionine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and others related to cell signaling and DNA repair (Benjamini and Yekutieli adjusted p ≤0.01). Interestingly, a recent study reporting metabolic responses and pathway changes of mammalian cells showed significant alteration of phenylalanine, tyrosine, and tryptophan biosynthesis pathway in response to changes in culture conditions and media composition …”

Using MVDA with stoichiometric balances to optimize amino acid concentrations in chemically defined CHO cell culture medium for improved culture performance

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