Metabolism of PER.C6™ cells cultivated under fed-batch conditions at low glucose and glutamine levels

Biotechnology and Bioengineering

Volumn 94, Issue 1, 2006, Pages 139-150

  Maranga, Luis ^a   Goochee, Charles F ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Fed batch; Glucose; Glutamine; Metabolic shift; PER.C6 cells

Indexed keywords

AMMONIUM COMPOUNDS; BIOREACTORS; CELL CULTURE; GLUCOSE; METABOLISM; NUTRITION; SYNTHESIS (CHEMICAL);

FED-BATCH; GLUTAMINE; METABOLIC SHIFTS; PER.C6™ CELLS;

CYTOLOGY;

AMMONIA; GLUCOSE; GLUTAMINE; LACTIC ACID; NONESSENTIAL AMINO ACID; AMINO ACID; OXYGEN;

AEROBIC METABOLISM; AMINO ACID METABOLISM; ARTICLE; BIOREACTOR; CELL CULTURE; CELL ENERGY; CELL GROWTH; CELL METABOLISM; CELL STRAIN HEK293; CONCENTRATION (PARAMETERS); DEGRADATION; ENERGY METABOLISM; FED BATCH CULTURE; GLUCOSE METABOLISM; HUMAN; HUMAN CELL; MATHEMATICAL COMPUTING; NUTRIENT; ADENOVIRUS; CELL COUNT; CELL LINE; CELL SURVIVAL; CHEMISTRY; COMPARATIVE STUDY; CULTURE MEDIUM; CULTURE TECHNIQUE; CYTOLOGY; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PRENATAL DEVELOPMENT; RETINA; TIME; VIROLOGY; VIRUS CELL TRANSFORMATION;

MAMMALIA;

ADENOVIRIDAE; AMINO ACIDS; AMMONIA; BIOREACTORS; CELL COUNT; CELL CULTURE TECHNIQUES; CELL LINE, TRANSFORMED; CELL SURVIVAL; CELL TRANSFORMATION, VIRAL; CULTURE MEDIA; CULTURE MEDIA, SERUM-FREE; ENERGY METABOLISM; GLUCOSE; GLUTAMINE; HUMANS; LACTIC ACID; OXYGEN; RETINA; TIME FACTORS;

EID: 33646549629     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.20890     Document Type: Article

References (52)

1. Altamirano C, Paredes C, Cairo JJ, Godia F. 2000. Improvement of CHO cell culture medium formulation: Simultaneous substitution of glucose and glutamine. Biotechnol Prog 16:69-75.
2. Andersen DC, Goochee CF. 1995. The effect of ammonia on the O-linked glycosylation of granulocyte colony-stimulating factor produced by Chinese hamster ovary cells. Biotechnol Bioeng 47:96-105.
3. Bebbington CR, Renner G, Thomson S, King D, Abrams D, Yarranton GT. 1992. High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. Biotechnology (N Y) 10:169-175.
4. Bibila TA, Robinson DK. 1995. In pursuit of the optimal fed-batch process for monoclonal antibody production. Biotechnol Prog 11:1-13.
5. Bibila TA, Ranucci CS, Glazomitsky K, Buckland BC, Aunins JG. 1994. Monoclonal antibody process development using medium concentrates. Biotechnol Prog 10:87-96.
6. Chen K, Liu Q, Xie L, Sharp PA, Wang DI. 2001. Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production. Biotechnol Bioeng 72:55-61.
7. Christie A, Butler M. 1999. The adaptation of BHK cells to a non-ammoniagenic glutamate-based culture medium. Biotechnol Bioeng 64:298-309.
8. Chu L, Robinson DK. 2001. Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol 12:180-187.
9. Cruz HJ, Ferreira AS, Freitas CM, Moreira JL, Carrondo MJ. 1999a. Metabolic responses to different glucose and glutamine levels in baby hamster kidney cell culture. Appl Microbiol Biotechnol 51:579-585.
10. Cruz HJ, Moreira JL, Carrondo MJ. 1999b. Metabolic shifts by nutrient manipulation in continuous cultures of BHK cells. Biotechnol Bioeng 66:104-113.
11. Cruz HJ, Freitas CM, Alves PM, Moreira JL, Carrondo MJ. 2000. Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells. Enzyme Microb Technol 27:43-52.
12. Doverskog M, Ljunggren J, Ohman L, Haggstrom L. 1997. Physiology of cultured animal cells. J Biotechnol 59:103-115.
13. Europa AF, Gambhir A, Fu PC, Hu WS. 2000. Multiple steady states with distinct cellular metabolism in continuous culture of mammalian cells. Biotechnol Bioeng 67:25-34.
14. Fallaux FJ, Bout A, van der Velde I, van den Wollenberg DJ, Hehir KM, Keegan J, Auger C, Cramer SJ, van Ormondt H, van der Eb AJ, Valerio D, Hoeben RC. 1998. New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 9:1909-1917.
15. Gambhir A, Europa AF, Hu WS. 1999. Alteration of cellular metabolism by consecutive fed-batch cultures of mammalian cells. J Bioscience Bioeng 87:805-810.
16. Genzel Y, Riffer JB, König S, Alt R, Reichl U. 2005. Substitution of glutamine by pyruvate to reduce ammonia formation and growth inhibition of mammalian cells. Biotechnol Prog 21:58-69.
17. Häggström L, Ljunggren J, Ohman L. 1996. Metabolic engineering of animal cells. Ann N Y Acad Sci 782:40-52.
18. Irani N, Wirth M, van Den Heuvel J, Wagner R. 1999. Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction. Biotechnol Bioeng 66:238-246.
19. Irani N, Beccaria AJ, Wagner R. 2002. Expression of recombinant cytoplasmic yeast pyruvate carboxylase for the improvement of the production of human erythropoietin by recombinant BHK-21 cells. J Biotechnol 93:269-282.
20. Jones D, Kroos N, Anema R, van Montfort B, Vooys A, van der Kraats S, van der Helm E, Smits S, Schouten J, Brouwer K, Lagerwerf F, van Berkel P, Opstelten DJ, Logtenberg T, Bout A. 2003. High-level expression of recombinant IgG in the human cell line per.c6. Biotechnol Prog 19:163-168.
21. Kurokawa H, Park YS, Iijima S, Kobayashi T. 1994. Growth characteristics in fed-batch culture of hybridoma cells with control of glucose and glutamine concentrations. Biotechnol Bioeng 44:95-103.
22. Kyung YS, Hu WS. 1995. Enahced productivity of Protein C by recombinant human cells in automated fed-batch cultures. Cytotechnol 17:109-115.
23. Lao MS, Toth D. 1997. Effects of ammonium and lactate on growth and metabolism of a recombinant Chinese hamster ovary cell culture. Biotechnol Prog 13:688-691.
24. Lee YY, Yap MG, Hu WS, Wong KT. 2003. Low-glutamine fed-batch cultures of 293-HEK serum-free suspension cells for adenovirus production. Biotechnol Prog 19:501-509.
25. Ljunggren J, Häggström L. 1994. Catabolic control of hybridoma cells by glucose and glutamine limited fed batch cultures. Biotechnol Bioeng 44:808-818.
26. Maranga L, Aunins JG, Zhou W. 2005. Characterization of changes in PER.C6(TM) cellular metabolism during growth and propagation of a replication-deficient adenovirus vector. Biotechnol Bioeng 90:645-655.
27. McDermott RH, Butler M. 1993. Uptake of glutamate, not glutamine synthetase, regulates adaptation of mammalian cells to glutamine-free medium. J Cell Sci 104(Pt 1):51-58.
28. Nadeau I, Jacob D, Perrier M, Kamen A. 2000a. 293SF metabolic flux analysis during cell growth and infection with an adenoviral vector. Biotechnol Prog 16:872-884.
29. Nadeau I, Sabatie J, Koehl M, Perrier M, Kamen A. 2000b. Human 293 cell metabolism in low glutamine-supplied culture: Interpretation of metabolic changes through metabolic flux analysis. Metab Eng 2:277-292.
30. Nadeau I, Gilbert PA, Jacob D, Perrier M, Kamen A. 2002. Low-protein medium affects the 293SF central metabolism during growth and infection with adenovirus. Biotechnol Bioeng 77:91-104.
31. Neermann J, Wagner R. 1996. Comparative analysis of glucose and glutamine metabolism in transformed mammalian cell lines, insect and primary liver cells. J Cell Physiol 166:152-169.
32. Newland M, Kamal MN, Greenfield PF, Nielsen LK. 1994. Ammonia inhibition of hybridomas propagated in batch, fed-batch, and continuous culture. Biotechnol Bioeng 43:434-438.
33. Omasa T, Higashiyama KI, Shioya I, Suga KI. 1991. Effects of lactate concentration on hybridoma culture in lactate-controlled fed-batch operation. Biotechnol Bioeng 39:556-564.
34. Ozturk SS. 1999. Ammonia toxicity, animal cells. In: Flickinger MC, Drew SW, editors. Encyclopedia of bioprocess technology-Fermentation, biocatalysis, and bioseparation. Hoboken: John Wiley & Sons, pp 121-136.
35. Ozturk SS, Palsson BO. 1990. Chemical decomposition of glutamine in cell culture media: Effect of media type, pH, and serum concentration. Biotechnol Prog 6:121-128.
36. Ozturk SS, Palsson BO. 1991. Growth, metabolic, and antibody production kinetics of hybridoma cell culture: 1. Analysis of data from controlled batch reactors. Biotechnol Prog 7:471-480.
37. Pau MG, Ophorst C, Koldijk MH, Schouten G, Mehtali M, Uytdehaag F. 2001. The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Vaccine 19:2716-2721.
38. Ryll T, Valley U, Wagner R. 1994. Biochemistry of growth inhibition by ammonium ions in mammalian cells. Biotechnol Bioeng 44:184-193.
39. Schneider M, Marison IW, vonStockar U. 1996. The importance of ammonia in mammalian cell culture. J Biotechnol 46:161-185.
40. Siegwart P, Cote J, Male K, Luong JH, Ferner M, Kamen A. 1999. Adaptive control at low glucose concentration of HEK-293 cell serum-free cultures. Biotechnol Prog 15:608-616.
41. Street JC, Delort AM, Braddock PS, Brindle KM. 1993. A 1H/15N n.m.r. study of nitrogen metabolism in cultured mammalian cells. Biochem J 291(Pt2):485-492.
42. van Wandelen C, Cohen SA. 1997. Using quaternary high-performance liquid chromatography eluent systems for separating 6-aminoquinolyl-N- hydroxysuccinimidyl carbamate-derivatized amino acid mixtures. J Chromatogr A 763:11-22.
43. - cotransporter induces apoptosis in hybridoma cells. Biotechnol Lett 20:87-90.
44. Xie L, Wang DI. 1996. High cell density and high monoclonal antibody production through medium design and rational control in a bioreactor. Biotechnol Bioeng 51:725-729.
45. Xie L, Wang DI. 1997. Integrated approaches to the design of media and feeding strategies for fed-batch cultures of animal cells. Trends Biotechnol 15:109-113.
46. Xie L, Nyberg G, Gu X, Li H, Mollborn F, Wang DIC. 1997. Gamma-interferon production and quality in stoichiometric fed-batch cultures of Chinese hamster ovary (CHO) cells under serum-free conditions. Biotechnol Bioeng 56:577-582.
47. Xie L, Pilbrough W, Metallo C, Zhong T, Pikus L, Leung J, Aunins JG, Zhou W. 2002. Serum-free suspension cultivation of PER.C6(R) cells and recombinant adenovirus production under different pH conditions. Biotechnol Bioeng 80:569-579.
48. Xie L, Metallo C, Warren J, Pilbrough W, Peltier J, Zhong T, Pikus L, Yancy A, Leung J, Aunins JG, Zhou W. 2003a. Large-scale propagation of a replication-defective adenovirus vector in stirred-tank bioreactor PER.C6 cell culture under sparging conditions. Biotechnol Bioeng 83:45-52.
49. Xie L, Zhou W, Robinson DK. 2003b. Protein production by large-scale mammalian cell culture. In: Makrides SC, editor. Gene transfer and expression in mammalian cells. Amsterdam: Elsevier Science B.V. pp 605-623.
50. Zeng AP, Hu WS, Deckwer WD. 1998. Variation of stoichiometric ratios and their correlation for monitoring and control of animal cell cultures. Biotechnol Prog 14:434-441.
51. Zhou W, Rehm J, Hu WS. 1995. High viable cell concentration fed-batch cultures of hybridoma cells through on-line nutrient feeding. Biotechnol Bioeng 46:579-587.
52. Zhou W, Chen C-C, Buckland BC, Aunins JG. 1997. Fed-batch culture of recombinant NSO myeloma cells with high monoclonal antibody production. Biotechnol Bioeng 55:783-792.