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Quantitative intracellular flux modeling and applications in biotherapeutic development and production using CHO cell cultures
Author(s) -
Huang Zhuangrong,
Lee DongYup,
Yoon Seongkyu
Publication year - 2017
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.26384
Subject(s) - chinese hamster ovary cell , bioprocess , metabolic flux analysis , flux balance analysis , biopharmaceutical , biochemical engineering , flux (metallurgy) , metabolic engineering , bioprocess engineering , computational biology , constraint (computer aided design) , systems biology , intracellular , computer science , cell culture , biological system , biology , microbiology and biotechnology , chemistry , biochemistry , engineering , metabolism , enzyme , mechanical engineering , paleontology , genetics , organic chemistry
Chinese hamster ovary (CHO) cells have been widely used for producing many recombinant therapeutic proteins. Constraint‐based modeling, such as flux balance analysis (FBA) and metabolic flux analysis (MFA), has been developing rapidly for the quantification of intracellular metabolic flux distribution at a systematic level. Such methods would produce detailed maps of flows through metabolic networks, which contribute significantly to better understanding of metabolism in cells. Although these approaches have been extensively established in microbial systems, their application to mammalian cells is sparse. This review brings together the recent development of constraint‐based models and their applications in CHO cells. The further development of constraint‐based modeling approaches driven by multi‐omics datasets is discussed, and a framework of potential modeling application in cell culture engineering is proposed. Improved cell culture system understanding will enable robust developments in cell line and bioprocess engineering thus accelerating consistent process quality control in biopharmaceutical manufacturing.