2010
DOI: 10.1016/j.jbiotec.2010.03.018
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Metabolomics-driven approach for the improvement of Chinese hamster ovary cell growth: Overexpression of malate dehydrogenase II

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Cited by 89 publications
(56 citation statements)
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“…These platforms include optimized vector systems, selection and amplification protocols, sophisticated and partly automated screening procedures as well as media and process platforms tailor-made for the individual needs of the CHO host cell clone. Moreover, transcriptomics (Nissom et al, 2006;Birzele et al, 2010;Kantardjieff et al, 2010), proteomics (Meleady, 2007;Pascoe et al, 2007) and metabolomics approaches (Nolan and Lee, 2011;Chong et al, 2010) have been used to elucidate the regulatory mechanisms within this host cell and genetic modifications might have been introduced to enhance viability, cellular productivity or other beneficial properties (for review, see also Kuystermans et al, 2007;Mohan et al, 2008). Thus, high titers achieved through effec- tive gene amplification as well as the know-how built around them made DHFR-deficient CHO cells very successful production host cells for the biopharmaceutical industry.…”
Section: Introductionmentioning
confidence: 99%
“…These platforms include optimized vector systems, selection and amplification protocols, sophisticated and partly automated screening procedures as well as media and process platforms tailor-made for the individual needs of the CHO host cell clone. Moreover, transcriptomics (Nissom et al, 2006;Birzele et al, 2010;Kantardjieff et al, 2010), proteomics (Meleady, 2007;Pascoe et al, 2007) and metabolomics approaches (Nolan and Lee, 2011;Chong et al, 2010) have been used to elucidate the regulatory mechanisms within this host cell and genetic modifications might have been introduced to enhance viability, cellular productivity or other beneficial properties (for review, see also Kuystermans et al, 2007;Mohan et al, 2008). Thus, high titers achieved through effec- tive gene amplification as well as the know-how built around them made DHFR-deficient CHO cells very successful production host cells for the biopharmaceutical industry.…”
Section: Introductionmentioning
confidence: 99%
“…For example, a liquid chromatography mass spectrometry (LCMS) based study found that acetylphenylalanine and dimethylarginine accumulate when CHO fed-batch culture entered stationary phase, which corresponds to their detrimental effect to cell growth (Chong et al 2009). Later, the same group reported that aspartate supplied in the medium formulation resulted in malate efflux leading to higher cell density and improved product titer of the culture system in study (Chong et al 2010).…”
Section: Discussionmentioning
confidence: 95%
“…Some lactate may be obtained from malate that is secreted out of the mitochondria from TCA cycle. The secretion of malate occurs either to provide NADPH demand for cells during exponential phase or due to the rate limiting process of malate conversion to oxaloacetate in TCA cycle [26]. The conversion of malate to pyruvate in the cytoplasm is mediated by malic enzyme I (ME-I) or by phosphoenolpyruvate carboxykinase (PEPCK) enzyme.…”
Section: Glutaminementioning
confidence: 99%