Exometabolome profiling reveals activation of the carnitine buffering pathway in fed‐batch cultures of CHO cells co‐fed with glucose and lactic acid

2021 ◽  
Author(s):  
Johanna Vappiani ◽  
Tom Eyster ◽  
Keegan Orzechowski ◽  
Diana Ritz ◽  
Pramthesh Patel ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Cho Cells ◽  
Fed Batch ◽  
Batch Cultures

RNAi suppression of Bax and Bak enhances viability in fed-batch cultures of CHO cells

2006 ◽  
Vol 8 (6) ◽  
pp. 509-522 ◽  
Author(s):  
Sing Fee Lim ◽  
Kok Hwee Chuan ◽  
Sen Liu ◽  
Sophia O.H. Loh ◽  
Beatrice Y.F. Chung ◽  
...  
Keyword(s):  
Cho Cells ◽  
Fed Batch ◽  
Batch Cultures

scholarly journals Lactate Control Enhances Growth Advantage in Fed-batch Cultures of Metabolically Engineered CHO Cells with Reduced Novel Growth-inhibitory Compound Formation

2021 ◽  
Author(s):  
Quentin Bethune ◽  
Cameron Harrington ◽  
Bhanu Mulukutla
Keyword(s):  
Amino Acid ◽  
Cho Cells ◽  
Fed Batch ◽  
Compound Formation ◽  
Knock Out ◽  
Batch Cultures ◽  
Growth Inhibitory ◽  
Inhibitory Compound ◽  
Cell Densities ◽  
Produce Amino Acid

CHO cells have been recently shown to produce amino acid catabolism derived byproducts, which accumulate in fed-batch cultures to growth-inhibitory levels. Residual amino acid limitation or genetic engineering strategies have been successfully employed to suppress production of these novel growth inhibitory metabolic byproducts. However, the growth advantage attained due to suppression of these metabolic byproducts in fed-batch cultures is more pronounced when lactate accumulation is also controlled. BCAT1 knock-out (KO) CHO cells, which produce negligible levels of the metabolic byproducts isovalerate, isobutyrate and 2-methylbutyrate, grow to significantly higher peak cell densities in fed-batch cultures with lactate control (HiPDOG) as compared to cultures without lactate control. Henceforth, strategies involving novel metabolic byproduct control should preferably include lactate control to more easily assess the enhanced cell growth and productivities attainable.

Specific inhibition of caspase-8 and -9 in CHO cells enhances cell viability in batch and fed-batch cultures

2007 ◽  
Vol 9 (5-6) ◽  
pp. 406-418 ◽  
Author(s):  
Chee Yong Yun ◽  
Sen Liu ◽  
Sing Fee Lim ◽  
Tianhua Wang ◽  
Beatrice Y.F. Chung ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cho Cells ◽  
Caspase 8 ◽  
Specific Inhibition ◽  
Fed Batch ◽  
Batch Cultures

scholarly journals Bacteriocin Production with Lactobacillus amylovorus DCE 471 Is Improved and Stabilized by Fed-Batch Fermentation

2000 ◽  
Vol 66 (2) ◽  
pp. 606-613 ◽  
Author(s):  
Raf Callewaert ◽  
Luc De Vuyst
Keyword(s):  
Lactic Acid ◽  
Nitrogen Source ◽  
Culture Conditions ◽  
Bacteriocin Production ◽  
Fed Batch ◽  
Batch Cultures ◽  
Lactobacillus Amylovorus ◽  
Complex Nitrogen Source ◽  
High Concentrations ◽  
Substrate Addition

ABSTRACT Amylovorin L471 is a small, heat-stable, and hydrophobic bacteriocin produced by Lactobacillus amylovorus DCE 471. The nutritional requirements for amylovorin L471 production were studied with fed-batch fermentations. A twofold increase in bacteriocin titer was obtained when substrate addition was controlled by the acidification rate of the culture, compared with the titers reached with constant substrate addition or pH-controlled batch cultures carried out under the same conditions. An interesting feature of fed-batch cultures observed under certain culture conditions (constant feed rate) is the apparent stabilization of bacteriocin activity after obtaining maximum production. Finally, a mathematical model was set up to simulate cell growth, glucose and complex nitrogen source consumption, and lactic acid and bacteriocin production kinetics. The model showed that bacterial growth was dependent on both the energy and the complex nitrogen source. Bacteriocin production was growth associated, with a simultaneous bacteriocin adsorption on the producer cells dependent on the lactic acid accumulated and hence the viability of the cells. Both bacteriocin production and adsorption were inhibited by high concentrations of the complex nitrogen source.

scholarly journals Production of Butyrate and Branched Chain Amino Acid Catabolic Byproducts by CHO Cells in Fed-batch Culture Enhances their Specific Productivity

2021 ◽  
Author(s):  
Cameron Harrington ◽  
Taylor Kalomeris ◽  
Michaela Jacobs ◽  
Gregory Hiller ◽  
Bhanu Chandra Mulukutla
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Cho Cells ◽  
Lactate Production ◽  
Specific Productivity ◽  
Fed Batch ◽  
Cho Cell ◽  
Batch Cultures ◽  
Branched Chain Amino Acid ◽  
Branched Chain

Chinese hamster ovary (CHO) cells in fed-batch cultures produce several metabolic byproducts derived from amino acid catabolism, some of which accumulate to growth inhibitory levels. Controlling the accumulation of these byproducts has been shown to significantly enhance cell proliferation. Interestingly, some of these byproducts have physiological roles that go beyond inhibition of cell proliferation. In this study, we show that, in CHO cell fed-batch cultures, branched chain amino acid (BCAA) catabolism contributes to the formation of butyrate, a novel byproduct that is also a well-established specific productivity enhancer. Further, the other byproducts of BCAA catabolism, isovalerate and isobutyrate, which accumulate in CHO cell fed-batch cultures also enhance specific productivity. Additionally, the rate of production of these BCAA catabolic byproducts was negatively correlated with glucose uptake and lactate production rates. Limiting glucose supply to suppress glucose uptake and lactate production, like in case of fed-batch cultures employing HiPDOG technology, significantly enhances BCAA catabolic byproduct accumulation resulting in higher specific productivities.

scholarly journals Caspase activation, sialidase release and changes in sialylation pattern of recombinant human erythropoietin produced by CHO cells in batch and fed-batch cultures

2006 ◽  
Vol 51 (2) ◽  
pp. 67-79 ◽  
Author(s):  
Kok Hwee Chuan ◽  
Sing Fee Lim ◽  
Laurent Martin ◽  
Chee Yong Yun ◽  
Sophia O. H. Loh ◽  
...  
Keyword(s):  
Cho Cells ◽  
Recombinant Human Erythropoietin ◽  
Caspase Activation ◽  
Fed Batch ◽  
Batch Cultures ◽  
Human Erythropoietin
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