Access the full text.
Sign up today, get DeepDyve free for 14 days.
Su‐Jeong Hwang, S. Yoon, G. Koh, G. Lee (2011)
Effects of culture temperature and pH on flag-tagged COMP angiopoietin-1 (FCA1) production from recombinant CHO cells: FCA1 aggregationApplied Microbiology and Biotechnology, 91
J. Osman, J. Birch, J. Varley (2001)
The response of GS-NS0 myeloma cells to pH shifts and pH perturbations.Biotechnology and bioengineering, 75 1
C Goudar, R Biener, J Piret, K. Konstantinov (2014)
Animal Cell Biotechnology
S. Kuwae, Toyoo Ohda, H. Tamashima, H. Miki, Kaoru Kobayashi (2005)
Development of a fed-batch culture process for enhanced production of recombinant human antithrombin by Chinese hamster ovary cells.Journal of bioscience and bioengineering, 100 5
R. Heijden, B. Romein, J. Heijnen, C. Hellinga, K. Luyben (1994)
Linear constraint relations in biochemical reaction systems: II. Diagnosis and estimation of gross errorsBiotechnology and Bioengineering, 43
T. Mehmood, K. Liland, L. Snipen, S. Sæbø (2012)
A review of variable selection methods in Partial Least Squares RegressionChemometrics and Intelligent Laboratory Systems, 118
Jochen Schaub, C. Clemens, H. Kaufmann, T. Schulz (2012)
Advancing biopharmaceutical process development by system-level data analysis and integration of omics data.Advances in biochemical engineering/biotechnology, 127
T. Schmidberger, C. Posch, A. Sasse, Carina Gülch, R. Huber (2015)
Progress toward forecasting product quality and quantity of mammalian cell culture processes by performance‐based modelingBiotechnology Progress, 31
Dénes Zalai, Aydin Golabgir, P. Wechselberger, A. Putics, C. Herwig (2015)
Advanced Development Strategies for Biopharmaceutical Cell Culture Processes.Current pharmaceutical biotechnology, 16 11
Jason Dean, Pranhitha Reddy (2013)
Metabolic analysis of antibody producing CHO cells in fed‐batch productionBiotechnology and Bioengineering, 110
Ryan Nolan, Kyongbum Lee (2011)
Dynamic model of CHO cell metabolism.Metabolic engineering, 13 1
Ningning Ma, JoAnn Ellet, C. Okediadi, P. Hermes, E. McCormick, S. Casnocha (2009)
A single nutrient feed supports both chemically defined NS0 and CHO fed‐batch processes: Improved productivity and lactate metabolismBiotechnology Progress, 25
B. Mulukutla, M. Gramer, Wei-Shou Hu (2012)
On metabolic shift to lactate consumption in fed-batch culture of mammalian cells.Metabolic engineering, 14 2
Jun Luo, N. Vijayasankaran, Jennifer Autsen, Rodell Santuray, Terry Hudson, A. Amanullah, Feng Li (2012)
Comparative metabolite analysis to understand lactate metabolism shift in Chinese hamster ovary cell culture processBiotechnology and Bioengineering, 109
J. Wahrheit, J. Niklas, E. Heinzle (2014)
Metabolic control at the cytosol-mitochondria interface in different growth phases of CHO cells.Metabolic engineering, 23
S. Abu-Absi, Sen Xu, H. Graham, Nimish Dalal, Marcus Boyer, K. Dave (2014)
Cell culture process operations for recombinant protein production.Advances in biochemical engineering/biotechnology, 139
Srinivas Karra, B. Sager, M. Karim (2010)
Multi-Scale Modeling of Heterogeneities in Mammalian Cell Culture ProcessesIndustrial & Engineering Chemistry Research, 49
Marija Ivarsson, H. Noh, M. Morbidelli, M. Šoóš (2015)
Insights into pH‐induced metabolic switch by flux balance analysisBiotechnology Progress, 31
J. Niklas, Eva Schräder, V. Sandig, T. Noll, E. Heinzle (2010)
Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysisBioprocess and Biosystems Engineering, 34
M. Vergara, S. Becerra, J. Berrios, N. Osses, J. Reyes, M. Rodríguez-Moyá, R. Gonzalez, C. Altamirano (2014)
Differential Effect of Culture Temperature and Specific Growth Rate on CHO Cell Behavior in Chemostat CulturePLoS ONE, 9
Zizhuo Xing, Brian Kenty, I. Koyrakh, Michael Borys, Shih-Hsie Pan, Z. Li (2011)
Optimizing amino acid composition of CHO cell culture media for a fusion protein productionProcess Biochemistry, 46
W. Ahn, M. Antoniewicz (2012)
Towards dynamic metabolic flux analysis in CHO cell culturesBiotechnology Journal, 7
F. Zagari, M. Jordan, Matthieu Stettler, H. Broly, F. Wurm (2013)
Lactate metabolism shift in CHO cell culture: the role of mitochondrial oxidative activity.New biotechnology, 30 2
Natalia Gomez, J. Ouyang, Mary Nguyen, Abigail Vinson, Andy Lin, Inn Yuk (2010)
Effect of temperature, pH, dissolved oxygen, and hydrolysate on the formation of triple light chain antibodies in cell cultureBiotechnology Progress, 26
S. Yoon, Sung Kim, Ji Song, G. Lee (2006)
Biphasic culture strategy for enhancing volumetric erythropoietin productivity of Chinese hamster ovary cellsEnzyme and Microbial Technology, 39
Kashif Sheikh, Jochen Förster, L. Nielsen (2008)
Modeling Hybridoma Cell Metabolism Using a Generic Genome‐Scale Metabolic Model of Mus musculusBiotechnology Progress, 21
E. Trummer, Katharina Fauland, Silke Seidinger, Kornelia Schriebl, Christine Lattenmayer, R. Kunert, K. Vorauer-Uhl, R. Weik, N. Borth, H. Katinger, D. Müller (2006)
Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo‐Fc expressing CHO cells cultivated in controlled batch bioreactorsBiotechnology and Bioengineering, 94
M. Halperin, H. Connors, A. Relman, M. Karnovsky (1969)
Factors that control the effect of pH on glycolysis in leukocytes.The Journal of biological chemistry, 244 2
P. Ruffieux, U. Stockar, I. Marison (1998)
Measurement of volumetric (OUR) and determination of specific (qO2) oxygen uptake rates in animal cell cultures.Journal of biotechnology, 63 2
C. Goudar, R. Biener, J. Piret, K. Konstantinov (2014)
Metabolic flux estimation in mammalian cell cultures.Methods in molecular biology, 1104
Marija Ivarsson, T. Villiger, M. Morbidelli, M. Šoóš (2014)
Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation.Journal of biotechnology, 188
W. Ahn, M. Antoniewicz (2011)
Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry.Metabolic engineering, 13 5
Neil Templeton, Jason Dean, Pranhitha Reddy, Jamey Young (2013)
Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed‐batch CHO cell cultureBiotechnology and Bioengineering, 110
S. Yoon, S. Hwang, G. Lee (2004)
Enhancing Effect of Low Culture Temperature on Specific Antibody Productivity of Recombinant Chinese Hamster Ovary Cells: Clonal VariationBiotechnology Progress, 20
Verónica Martínez, Stefanie Dietmair, L. Quek, M. Hodson, P. Gray, L. Nielsen (2013)
Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption.Biotechnology and bioengineering, 110 2
M. Al-Fageeh, Rosalyn Marchant, Martin Carden, C. Smales (2006)
The cold-shock response in cultured mammalian cells: harnessing the response for the improvement of recombinant protein production.Biotechnology and bioengineering, 93 5
J. Wahrheit, Averina Nicolae, E. Heinzle (2014)
Dynamics of growth and metabolism controlled by glutamine availability in Chinese hamster ovary cellsApplied Microbiology and Biotechnology, 98
J Schaub, C Clemens, H Kaufmann, T. Schulz (2012)
Genomics and Systems Biology of Mammalian Cell Culture
A growing body of knowledge is available on the cellular regulation of overflow metabolism in mammalian hosts of recombinant protein production. However, to develop strategies to control the regulation of overflow metabolism in cell culture processes, the effect of process parameters on metabolism has to be well understood. In this study, we investigated the effect of pH and temperature shift timing on lactate metabolism in a fed‐batch Chinese hamster ovary (CHO) process by using a Design of Experiments (DoE) approach. The metabolic switch to lactate consumption was controlled in a broad range by the proper timing of pH and temperature shifts. To extract process knowledge from the large experimental dataset, we proposed a novel methodological concept and demonstrated its usefulness with the analysis of lactate metabolism. Time‐resolved metabolic flux analysis and PLS‐R VIP were combined to assess the correlation of lactate metabolism and the activity of the major intracellular pathways. Whereas the switch to lactate uptake was mainly triggered by the decrease in the glycolytic flux, lactate uptake was correlated to TCA activity in the last days of the cultivation. These metabolic interactions were visualized on simple mechanistic plots to facilitate the interpretation of the results. Taken together, the combination of knowledge‐based mechanistic modeling and data‐driven multivariate analysis delivered valuable insights into the metabolic control of lactate production and has proven to be a powerful tool for the analysis of large metabolic datasets. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1657–1668, 2015
Biotechnology Progress – Wiley
Published: Nov 1, 2015
Keywords: ; ; ; ;
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.