The impact of anti-apoptotic gene Bcl-2∆ expression on CHO central metabolism

Templeton, Neil; Lewis, A. C.; Dorai, Haimanti; Qian, Elaine A.; Campbell, Marguerite; Smith, Kevin D.; Lang, Stanley; Betenbaugh, Michael J.; Young, Jamey D.

doi:10.1016/j.ymben.2014.06.010

Cited by 49 publications

(46 citation statements)

References 52 publications

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“…Further support for increased oxidative activity or decreased glycolysis driving the lactate switch comes from Templeton et al (2014). Further support for increased oxidative activity or decreased glycolysis driving the lactate switch comes from Templeton et al (2014).…”

Section: Mitochondrial Activitymentioning

confidence: 95%

Mechanisms driving the lactate switch in Chinese hamster ovary cells

Hartley

Walker

Chung

et al. 2018

Biotech & Bioengineering

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The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch. The influence of pH, NAD /NADH, pyruvate availability and mitochondrial function on lactate consumption are explored. A hypothesis based on the cellular redox state is put forward to explain the onset of lactate consumption. Various techniques implemented to control the lactate switch, including manipulation of the culture environment, genetic engineering, and cell line selection are also discussed.

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Section: Mitochondrial Activitymentioning

confidence: 95%

Mechanisms driving the lactate switch in Chinese hamster ovary cells

Hartley

Walker

Chung

et al. 2018

Biotech & Bioengineering

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“…INST [48] INST [46] PWA [59] PWA [60] IST [56] INST [62] IST [64] INST [63] [9] FR [50] Single Cell FR/KFP [68] [53]…”

Section: Fluxes At Different Levels Of Biological Organization and Comentioning

confidence: 99%

How to measure metabolic fluxes: a taxonomic guide for 13 C fluxomics

Niedenführ

Wiechert

Nöh

2015

Current Opinion in Biotechnology

113

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“…For example, Majors et al [33] inhibited apoptosis by modifying GLUT1 and/or hexokinase expression, since a high glycolytic activity can slow the onset of apoptosis by improving energy efficiency [34]. Moreover, recent studies have altered glycosylation patterns by maintaining efficient glucose metabolism and avoiding accumulation of toxic byproducts, since central metabolism controls the supply of nucleotide sugar precursors [35, 36].…”

Section: Controlling Other Metabolic Pathways While Engineering Centrmentioning

confidence: 99%

Improvements in protein production in mammalian cells from targeted metabolic engineering

Richelle

Lewis

2017

Current Opinion in Systems Biology

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Bioprocess optimization has yielded powerful clones for biotherapeutic production. However, new genomic technologies allow more targeted approaches to cell line development. Here we review efforts to enhance protein production in mammalian cells through metabolic engineering. Most efforts aimed to reduce toxic byproducts accumulation to enhance protein productivity. However, recent work highlights the possibility of regulating other desirable traits (e.g., apoptosis and glycosylation) by targeting central metabolism since these processes are interconnected. Therefore, as we further detail the pathways underlying cell growth and protein production and deploy diverse algorithms for their analysis, opportunities will arise to move beyond simple cell line designs and facilitate cell engineering strategies with complex combinations of genes that together underlie a phenotype of interest.

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The impact of anti-apoptotic gene Bcl-2∆ expression on CHO central metabolism

Cited by 49 publications

References 52 publications

Mechanisms driving the lactate switch in Chinese hamster ovary cells

Mechanisms driving the lactate switch in Chinese hamster ovary cells

How to measure metabolic fluxes: a taxonomic guide for 13 C fluxomics

Improvements in protein production in mammalian cells from targeted metabolic engineering

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