Insights into pH-induced metabolic switch by flux balance analysis

Biotechnology Progress

Volumn 31, Issue 2, 2015, Pages 347-357

  Ivarsson, Marija ^a   Noh, Heeju ^a   Morbidelli, Massimo ^a   Soos, Miroslav ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

Flux balance analysis; Gene expression analysis; Lactate metabolism; Mammalian cell cultivation; PH

Indexed keywords

ANIMAL CELL CULTURE; GLUCOSE; MAMMALS; PH;

ATP PRODUCTION RATES; EXPONENTIAL GROWTH PHASE; FLUX BALANCE ANALYSIS; GENE EXPRESSION ANALYSIS; LACTATE METABOLISMS; MAMMALIAN CELL CULTIVATIONS; MAMMALIAN CELL CULTURE; METABOLIC FLUX ANALYSIS;

GENE EXPRESSION;

MAMMALIA;

ADENOSINE TRIPHOSPHATE; GLUCOSE; LACTIC ACID; MONOCLONAL ANTIBODY;

ANIMAL; CELL LINE; GENE EXPRESSION; HUMAN; HYBRIDOMA; INTRACELLULAR SPACE; METABOLIC FLUX ANALYSIS; METABOLISM; MOUSE; PH; PHYSIOLOGY; PROCEDURES;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTIBODIES, MONOCLONAL; CELL LINE; GENE EXPRESSION; GLUCOSE; HUMANS; HYBRIDOMAS; HYDROGEN-ION CONCENTRATION; INTRACELLULAR SPACE; LACTIC ACID; METABOLIC FLUX ANALYSIS; METABOLIC NETWORKS AND PATHWAYS; MICE;

EID: 84928182401     PISSN: 87567938     EISSN: 15206033     Source Type: Journal    
DOI: 10.1002/btpr.2043     Document Type: Article

References (49)

1. Ozturk SS, Hu W. Cell Culture Technology for Pharmaceutical and Cell-Based Therapies. New York: CRC Press; 2006.
2. De Jesus M, Wurm FM. Manufacturing recombinant proteins in kg-ton quantities using animal cells in bioreactors. E. J Pharma Biopharma. 2011;78:184-188.
3. Warburg O. On the origin of cancer cells. Science (New York, N.Y.). 1956;123:309-314.
4. Ahn WS, Antoniewicz MR. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metabolic Eng. 2011;13:598-609.
5. Leite TC, Coelho RG, Da Silva D, Coelho WS, Marinho-Carvalho MM, Sola-Penna M. Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice. FEBS Lett. 2011;585:92-98.
6. Mulukutla BC, Gramer M, Hu W-S. On metabolic shift to lactate consumption in fed-batch culture of mammalian cells. Metabolic Eng. 2012;14:138-149.
7. Lao MS, Toth D. Effects of ammonium and lactate on growth and metabolism of a recombinant Chinese hamster ovary cell culture. Biotechnol Prog. 1997;13:688-691.
8. Ozturk SS, Riley MR, Palsson BO. Effects of ammonia and lactate on hybridoma growth, metabolism, and antibody production. Biotechnol Bioeng. 1992;39:418-431.
9. Chen K, Liu Q, Xie L, Sharp PA, Wang DI. Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production. Biotechnol Bioeng. 2001;72:55-61.
10. Paredes C, Prats E, Cairó JJ, Azorín F, Cornudella L, Gòdia F. Modification of glucose and glutamine metabolism in hybridoma cells through metabolic engineering. Cytotechnology. 1999;30(1-3):85-93.
11. Dorai H, Kyung YS, Ellis D, Kinney C, Lin C, Jan D, Moore G, Betenbaugh MJ. Expression of anti-apoptosis genes alters lactate metabolism of Chinese Hamster Ovary cells in culture. Biotechnol Bioeng. 2009;103:592-608.
12. Cruz HJ, Ferreira AS, Freitas CM, Moreira JL, Carrondo MJ. Metabolic responses to different glucose and glutamine levels in baby hamster kidney cell culture. Appl Microbiol Biotechnol. 1999;51:579-585.
13. Zhou W, Rehm J, Hu WS. High viable cell concentration fed-batch cultures of hybridoma cells through on-line nutrient feeding. Biotechnol Bioeng. 1995;46:579-587.
14. Altamirano C, Illanes A, Becerra S, Cairó JJ, Gòdia F. Considerations on the lactate consumption by CHO cells in the presence of galactose. J Biotechnol. 2006;125:547-556.
15. Sheikholeslami Z, Jolicoeur M, Henry O. Elucidating the effects of postinduction glutamine feeding on the growth and productivity of CHO cells. Biotechnol Prog. 2014;30:535-546.
16. Li J, Wong CL, Vijayasankaran N, Hudson T, Amanullah A. Feeding lactate for CHO cell culture processes: impact on culture metabolism and performance. Biotechnol Bioeng. 2012;109:1173-1186.
17. Osman J, Birch J, Varley J. The response of GS-NS0 myeloma cells to pH shifts and pH perturbations. Biotechnol Bioeng. 2001;75:63-73.
18. Trummer E, Fauland K, Seidinger S, et al. Process parameter shifting. I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors. Biotechnol Bioeng. 2006;94:1033-1044.
19. Ahn WS, Antoniewicz MR. Parallel labeling experiments with [1, 2-(13)C]glucose and [U-(13)C]glutamine provide new insights into CHO cell metabolism. Metabolic Eng. 2013;15:34-47.
20. Covert MW, Palsson BO. Constraints-based models: Regulation of gene expression reduces the steady-state solution space. J Theoretical Biol. 2003;221:309-325.
21. Bonarius HP, Schmid G, Tramper J. Flux analysis of underdetermined metabolic networks: The quest for the missing constraints. Trends Biotechnol. 1997;15:308-314.
22. Quek L-E, Dietmair S, Krömer JO, Nielsen LK. Metabolic flux analysis in mammalian cell culture. Metabolic Eng. 2010;12:161-171.
23. Bonarius HP, Timmerarends B, De Gooijer CD, Tramper J. Metabolite-balancing techniques vs. 13C tracer experiments to determine metabolic fluxes in hybridoma cells. Biotechnol Bioeng. 1998;58(2-3):258-262.
24. Martínez VS, Dietmair S, Quek L-E, Hodson MP, Gray P, Nielsen LK. Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption. Biotechnol Bioeng. 2013;110:660-666.
25. Sengupta N, Rose ST, Morgan JA. Metabolic flux analysis of CHO cell metabolism in the late non-growth phase. Biotechnol Bioeng. 2011;108:82-92.
26. Dean J, Reddy P. Metabolic analysis of antibody producing CHO cells in fed-batch production. Biotechnol Bioeng. 2013;110:1735-1747.
27. Schoen RC, Bentley KL, Klebe RJ. Monoclonal antibody against human fibronectin which inhibits cell attachment. Hybridoma. 1982;1:99-108.
28. Greene J, Jr JH, Wikswo J. Rapid and precise determination of cellular amino acid flux rates using HPLC with automated derivatization with absorbance detection. Agilent Pub. 2009:1-8.
29. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protocols. 2008;3:1101-1108.
30. Varma A, Palsson BO. Metabolic Flux balancing: Basic concepts, scientific and practical use. Nat Biotechnol. 1994;12:994-998.
31. Niklas J, Schräder E, Sandig V, Noll T, Heinzle E. Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis. Bioprocess Biosyst Eng. 2011;34:533-545.
32. Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27-30.
33. Goudar CT, Joeris K, Konstantinov KB, Piret JM. Logistic equations effectively model mammalian cell batch and fed-batch kinetics by logically constraining the fit. Biotechnol Prog. 2005;21:1109-1118.
34. Bonarius HP, Hatzimanikatis V, Meesters KP, De Gooijer CD, Schmid G, Tramper J. Metabolic flux analysis of hybridoma cells in different culture media using mass balances. Biotechnol Bioeng. 1996;50:299-318.
35. Selvarasu S, Karimi IA, Ghim G-H, Lee D-Y. Genome-scale modeling and in silico analysis of mouse cell metabolic network. Mol Biosyst. 2010;6:152-161.
36. Sheikh K, Förster J, Nielsen LK. Modeling hybridoma cell metabolism using a generic genome-scale metabolic model of Mus musculus. Biotechnol Prog. 2005;21:112-121.
37. Savinell JM, Palsson BO. Network analysis of intermediary metabolism using linear optimization. J. Theoretical Biol. 1992;154:455-473.
38. Carinhas N, Bernal V, Teixeira AP, Carrondo MJ, Alves PM, Oliveira R. Hybrid metabolic flux analysis: combining stoichiometric and statistical constraints to model the formation of complex recombinant products. BMC Syst Biol. 2011;5:34.
39. Miller WM, Blanch HW, Wilke CR. A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: Effect of nutrient concentration, dilution rate, and pH. Biotechnol Bioeng. 1988;32:947-965.
40. Ozturk SS, Palsson BO. Growth, metabolic, and antibody production kinetics of hybridoma cell culture. II. Effects of serum concentration, dissolved oxygen concentration, and medium pH in a batch reactor. Biotechnol Prog. 1991;7:481-494.
41. Nolan RP, Lee K. Dynamic model of CHO cell metabolism. Metabolic Eng. 2011;13:108-124.
42. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC, Baltazar F. Role of monocarboxylate transporters in human cancers: State of the art. J Bioenerg Biomembr. 2012:127-139.
43. Burgess SC, Hausler N, Merritt M, et al. Impaired tricarboxylic acid cycle activity in mouse livers lacking cytosolic phosphoenolpyruvate carboxykinase. J Biol Chem. 2004;279:48941-48949.
44. Hakimi P, Yang J, Casadesus G, et al. Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J Biol Chem. 2007;282:32844-32855.
45. Yoon SK, Choi SL, Song JY, Lee GM. Effect of culture pH on erythropoietin production by Chinese hamster ovary cells grown in suspension at 32.5 and 37.0 degrees C. Biotechnol Bioeng. 2005;89:345-356.
46. Zanghi JA, Schmelzer AE, Mendoza TP, Knop RH, Miller WM. Bicarbonate concentration and osmolality are key determinants in the inhibition of CHO cell polysialylation under elevated pCO(2) or pH. Biotechnol Bioeng. 1999;65:182-191.
47. Muthing J, Kemminer SE, Conradt HS, et al. Effects of buffering conditions and culture pH on production rates and glycosylation of clinical phase I anti-melanoma mouse IgG3 monoclonal antibody R24. Biotechnol Bioeng. 2003;83:321-334.
48. Hossler P, Khattak SF, Li ZJ. Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology. 2009;19:936-949.
49. Langheinrich C, Nienow AW. Control of pH in large-scale, free suspension animal cell bioreactors: alkali addition and pH excursions. Biotechnol Bioeng. 1999;66:171-179.