Journal
METABOLIC ENGINEERING
Volume 12, Issue 2, Pages 161-171Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2009.09.002
Keywords
Metabolic flux analysis (MFA); Mammalian cells; Review; Constrained-based analysis; Hybridoma; CHO
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Mammalian cell culture metabolism is characterized by glucoglutaminolysis, that is, high glucose and glutamine uptake combined with a high rate of lactate and non-essential amino acid secretion. Stress associated with acid neutralization and ammonia accumulation necessitates complex feeding schemes and limits cell densities achieved in fed-batch culture. Conventional and constraint-based metabolic flux analysis has been successfully used to study the metabolic phenotype of mammalian cells in culture, while C-13 tracer analysis has been used to study small network models and validate assumptions of metabolism. Large-scale C-13 metabolic flux analysis, which is required to improve confidence in the network models and their predictions, remains a major challenge. Advances in both modeling and analytical techniques are bringing this challenge within sight. (C) 2009 Elsevier Inc. All rights reserved.
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