Probing the metabolism of an inducible mammalian expression system using extracellular isotopomer analysis

Journal of Biotechnology

Volumn 164, Issue 4, 2013, Pages 469-478

  Sheikholeslami, Zahra ^a   Jolicoeur, Mario ^a   Henry, Olivier ^a  

^a ÉCOLE POLYTECHNIQUE DE MONTRÉAL   (Canada)

Author keywords

13C metabolic flux analysis; CHO cells; Inducible expression; Recombinant protein

Indexed keywords

CHO CELL; EXTRACELLULAR AMINO ACIDS; FLUX ANALYSIS; INDUCIBLE EXPRESSION; INDUCIBLE EXPRESSION SYSTEMS; ISOTOPOMER DISTRIBUTIONS; RECOMBINANT PROTEIN EXPRESSION; RECOMBINANT PROTEIN PRODUCTIONS;

AMINO ACIDS; ANIMAL CELL CULTURE; ISOMERS; MAMMALS; MASS SPECTROMETRY; METABOLISM; RECOMBINANT PROTEINS;

ENZYME ACTIVITY;

ADENOSINE TRIPHOSPHATE; AMINO ACID; LACTIC ACID; PYRUVIC ACID; RECOMBINANT PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

AMINO ACID METABOLISM; ANIMAL CELL; ARTICLE; CATABOLISM; CITRIC ACID CYCLE; CONTROLLED STUDY; GENE EXPRESSION SYSTEM; GLUCOSE UTILIZATION; INDUCED HYPOTHERMIA; MAMMAL CELL; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS;

ADENOSINE TRIPHOSPHATE; AMINO ACIDS; ANIMALS; CARBON ISOTOPES; CELL COUNT; CHO CELLS; CRICETINAE; CRICETULUS; EXTRACELLULAR SPACE; KINETICS; LACTIC ACID; METABOLIC NETWORKS AND PATHWAYS; MOLECULAR BIOLOGY; NADP; SYSTEMS BIOLOGY;

MAMMALIA;

EID: 84875603563     PISSN: 01681656     EISSN: 18734863     Source Type: Journal    
DOI: 10.1016/j.jbiotec.2013.01.025     Document Type: Article

References (44)

1. Ahn W.S., Antoniewicz M.R. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metabolic Engineering 2011, 13:598-609.
2. Altamirano C., Illanes A., Becerra S., Cairo J.J., Godia F. Considerations on the lactate consumption by CHO cells in the presence of galactose. Journal of Biotechnology 2006, 125:547-556.
3. Altamirano C., Illanes A., Casablancas A., Gamez X., Cairo J.J., Godia C. Analysis of CHO cells metabolic redistribution in a glutamate-based defined medium in continuous culture. Biotechnology Progress 2001, 17:1032-1041.
4. Antoniewicz M.R., Kelleher J.K., Stephanopoulos G. Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements. Metabolic Engineering 2006, 8:324-337.
5. Antoniewicz M.R., Kelleher J.K., Stephanopoulos G. Elementary metabolite unites (EMU): a novel framework for modeling isotopic distributions. Metabolic Engineering 2007, 9:68-86.
6. Baughman A.C., Huang X.Q., Sharfstein S.T., Martin L.L. On the dynamic modeling of mammalian cell metabolism and mAb production. Computers and Chemical Engineering 2010, 34:210-222.
7. Boghigian B.A., Seth G., Kiss R., Pfeifer B.A. Metabolic flux analysis and pharmaceutical production. Metabolic Engineering 2010, 12:81-95.
8. Bonarius H.P., Ozemre A., Timmerarends B., Skrabal P., Tramper J., Schmid G., Heinzle E. Metabolic-flux analysis of continuously cultured hybridoma cells using (13)CO(2) mass spectrometry in combination with (13)C-lactate nuclear magnetic resonance spectroscopy and metabolite balancing. Biotechnology and Bioengineering 2001, 74:528-538.
9. Dalm M.C.F., Lamers P.P., Cuijten S.M.R., Tjeerdsma A.M., Grunsven W.M.J., Tramper J., Martens D.E. Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion bioreactor: metabolic analysis. Biotechnology Progress 2007, 23:560-569.
10. Deshpande R., Yang T.H., Heinzle E. Towards a metabolic and isotopic steady state in CHO batch cultures for reliable isotope-based metabolic profiling. Biotechnology Journal 2009, 4:247-263.
11. Dinnis D.M., Stansfield S.H., Schlatter S., Smales C.M., Alete D., Birch J.R., Racher A.J., Marshall C.T., Nielsen L.K., James D.C. Functional proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnology and Bioengineering 2006, 94:830-841.
12. Gaillet B., Gilbert R., Amziani R., Guilbault C., Gadoury C., Caron A.W., Mullick A., Garnier A., Massie B. High-level recombinant protein productionin CHO cells using an adenoviral vector and the cumate gene switch. Biotechnology Progress 2007, 23:200-209.
13. Gaillet B., Gilbert R., Broussau S., Pilotte A., Malenfant F., Mullick A., Garnier A., Massie B. High-level recombinant protein production in CHO cells using lentiviral vectors and the cumate gene-switch. Biotechnology and Bioengineering 2010, 106:203-215.
14. Goudar C., Biener R., Boisart C., Heidemann R., Piret J., de Graaf A., Konstantinov K. Metabolic flux analysis of CHO cells in perfusion culture by metabolite balancing and 2D [13C,1H] Cosy NMR spectroscopy. Metabolic Engineering 2010, 12:138-149.
15. Henry O., Durocher Y. Enhanced glycoprotein production in HEK-293 cells expressing pyruvate carboxylase. Metabolic Engineering 2011, 13:499-507.
16. Henry O., Jolicoeur M., Kamen A. Unraveling the metabolism of HEK-293 cells using lactate isotopomer analysis. Bioprocess and Biosystems Engineering 2010, 34:263-273.
17. Henry O., Kwok E., Piret J.P. Simpler noninstrumented batch and semicontinuous cultures provide mammalian cell kinetic data comparable to continuous and perfusion cultures. Biotechnology Progress 2008, 24:921-931.
18. Heyland J., Blank L.M., Schmid A. Quantification of metabolic limitations during recombinant protein production in Escherichia coli. Journal of Biotechnology 2011, 155:178-184.
19. Heyland J., Fu J., Blank L.M., Schmid A. Carbon metabolism limits recombinant protein production in Pichia pastoris. Biotechnology and Bioengineering 2011, 108:1942-1953.
20. Hofmann U., Maier K., Niebel A., Vacun G., Reuss M., Mauch K. Identification of metabolic fluxes in hepatic cells from transient 13C-labeling experiments: part I. Experimental observations. Biotechnology and Bioengineering 2008, 100:344-354.
21. Maier K., Hofmann U., Reuss M., Mauch K. Identification of metabolic fluxes in hepatic cells from transient 13C-labeling experiments: part II. Flux estimation. Biotechnology and Bioengineering 2008, 100:355-370.
22. Mancuso A., Sharfstein S.T., Fernandez E.J., Clark D.S., Blanch H.W. Effect of extracellular glutamine concentration on primary and secondary metabolism of a murine hybridoma: an in vivo 13C nuclear magnetic resonance study. Biotechnology and Bioengineering 1998, 57:172-186.
23. Martens D.E. Metabolic Flux Analysis of Mammalian Cells. Systems Biology 2007, 275-299. Springer, The Netherlands. M. Al-Rubeai, M. Fussenegger (Eds.).
24. Meleady P., Doolan P., Henry M., Barron N., Keenan J., O'Sullivan F., Clarke C., Gammell P., Melville M.W., Leonard M., Clynes M. Sustained productivity in recombinant Chinese hamster ovary (CHO) cell lines: proteome analysis of the molecular basis for a process-related phenotype. BMC Biotechnology 2011, 11:78.
25. Metallo C.M., Walther J.L., Stephanopoulos G. Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. Journal of Biotechnology 2009, 144:167-174.
26. Mullick A., Xu Y., Warren R., Koutroumanis M., Guilbault C., Broussau S., Malenfant F., Bourget L., Lamoureux L., Lo R., Caron A.W., Pilotte A., Massie B. The cumate gene-switch: a system for regulated expression in mammalian cells. BMC Biotechnology 2006, 6.
27. Niklas J., Heinzle E. Metabolic Flux Analysis in Systems Biology of Mammalian Cells 2011, Springer, Berlin/Heidelberg, pp. 1-24.
28. Niklas J., Sandig V., Heinzle E. Metabolite channeling and compartmentation in the human cell line AGE1.HN determined by 13C labeling experiments and 13C metabolic flux analysis. Journal of Bioscience and Bioengineering 2011, 112:616-623.
29. Nolan R.P., Lee K. Dynamic model of CHO cell metabolism. Metabolic Engineering 2011, 13:108-124.
30. Ozturk S.S., Palsson B. Growth, metabolic, and antibody production kinetics of hybridoma cell culture: 2. Effects of serum concentration, dissolved oxygen concentration, and medium pH in a batch reactor. Biotechnology Progress 1991, 7:481-494.
31. Park J.H., Lee S.Y., Kim T.Y., Kim H.U. Application of systems biology for bioprocess development. Trends in Biotechnology 2008, 26:404-412.
32. Peuhkurinen K.J., Hiltunen J.K., Hassinen I.E. Metabolic compartmentation of pyruvate in the isolated perfused rat heart. Biochemical Journal 1983, 210:193-198.
33. Quek L.E., Dietmair S., Kromer J.O., Nielsen L.K. Metabolic flux analysis in mammalian cell culture. Metabolic Engineeering 2009, 12:161-172.
34. Quek L.E., Wittmann C., Nielsen L.K., Kromer J.O. OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis. Microbial Cell Factories 2009, 8.
35. Sengupta N., Rose S.T., Morgan J.A. Metabolic flux analysis of CHO cell metabolism in the late non-growth phase. Biotechnology and Bioengineering 2011, 108:82-92.
36. Selvarasu S., Ho Y.S., Chong W.P.K., Wong N.S.C., Yusufi F.N.K., Lee Y.Y., Yap M.G.S., Lee D.-Y. Combined in silico modeling and metabolomics analysis to characterize fed-batch CHO cell culture. Biotechnology and Bioengineering 2012, 109:1415-1429.
37. Stephanopoulos G., Aristodou A.A., Nielsen J. Metabolic Engineering: Principles and Methodologies 1998, Academic Press, San Diego.
38. Suthers P.F., Chang Y.J., Maranas C.D. Improved computational performance of MFA using elementary metabolite units and flux coupling. Metabolic Engineering 2010, 12:123-128.
39. Walsh G. Biopharmaceutical benchmarks 2010. Nature Biotechnology 2010, 28:917-924.
40. Walther J.L., Metallo C.M., Zhang J., Stephanopoulos G. Optimization of (13)C isotopic tracers for metabolic flux analysis in mammalian cells. Metabolic Engineering 2012, 14:162-171.
41. Xie L., Wang D. Material balance studies on animal cell metabolism using a stoechiometrically based reaction network. Biotechnology and Bioengineering 1996, 52:579-590.
42. Yallop C.A., Nørby P.L., Jensen R., Reinbach H., Svendsen I. Characterisation of G418-induced metabolic load in recombinant CHO and BHK cells: effect on the activity and expression of central metabolic enzymes. Cytotechnology 2003, 42:87-99.
43. Young J.D., Shastri A.A., Stephanopoulos G., Morgan J.A. Mapping photoautotrophic metabolism with isotopically nonstationary (13)C flux analysis. Metabolic Engineering 2011, 13:656-665.
44. Young J.D., Walther J.L., Antoniewicz M.R., Yoo H., Stephanopoulos G. An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis. Biotechnology and Bioengineering 2007, 99:686-699.