Metabolic analysis of antibody producing CHO cells in fed-batch production

Biotechnology and Bioengineering

Volumn 110, Issue 6, 2013, Pages 1735-1747

  Dean, Jason ^a   Reddy, Pranhitha ^a  

^a AMGEN INC   (United States)

Author keywords

Chinese hamster ovary cells; Fed batch mAb production; Metabolic flux analysis; Stable isotope tracers

Indexed keywords

ALTERNATIVE PRODUCTION SYSTEMS; CHINESE HAMSTER OVARY CELLS; DIFFERENTIAL REGULATION; EXPONENTIAL GROWTH PHASE; FED BATCHES; METABOLIC FLUX ANALYSIS; PHOSPHOENOLPYRUVATE CARBOXYKINASE; STABLE ISOTOPE TRACERS;

AMINO ACIDS; ANTIBODIES; CELL CULTURE; ENZYMES; GLUCOSE; ISOTOPES; METABOLISM; METABOLITES; PRODUCTIVITY; RECOMBINANT PROTEINS; TISSUE;

CELLS;

GLUCOSE; GLUTAMINE; LACTIC ACID; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PYRUVATE KINASE; STABLE ISOTOPE; TRICARBOXYLIC ACID;

ANIMAL CELL; ANTIBODY PRODUCTION; ANTIBODY TITER; ARTICLE; BIOSYNTHESIS; CELL GROWTH; CELL METABOLISM; CELL VIABILITY; CHO CELL; CITRIC ACID CYCLE; CONTROLLED STUDY; ENZYME REGULATION; FED BATCH CULTURE; GLUCOSE UTILIZATION; GLYCOLYSIS; IMMUNOGLOBULIN PRODUCING CELL; INTRACELLULAR SIGNALING; MOLECULAR WEIGHT; NONHUMAN; PHENOTYPE; REGULATORY MECHANISM;

AMINO ACIDS; ANIMALS; ANTIBODIES, MONOCLONAL; CELL CULTURE TECHNIQUES; CHO CELLS; CRICETINAE; CRICETULUS; GLUCOSE; ISOTOPE LABELING; LACTIC ACID; METABOLOME; PHOSPHOENOLPYRUVATE CARBOXYKINASE (ATP); PYRUVIC ACID; RECOMBINANT PROTEINS; RIBOSE;

CRICETULUS GRISEUS;

EID: 84876764895     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.24826     Document Type: Article

References (41)

1. Ahn WS, Antoniewicz MR. 2011. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metab Eng 13(5): 598-609.
2. 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(1): 69-75.
3. Bergmeyer HU, Gawehn K, Grassl M. 1974. In: Bergmeyer HU editor. Methods of enzymatic analysis, Vol. 1, 2nd edition. New York, NY: Academic press, Inc; p. 509-510.
4. Birch JR, Racher AJ. 2006. Antibody production. Adv Drug Deliv Rev 58(5-6): 671-685.
5. Boren J, Lee WN, Bassilian S, Centelles JJ, Lim S, Ahmed S, Boros LG, Cascante M. 2003. The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation. J Biol Chem 278(31): 28395-28402.
6. Burgess SC, Hausler N, Merritt M, Jeffrey FM, Storey C, Milde A, Koshy S, Lindner J, Magnuson MA, Malloy CR, Sherry AD. 2004. Impaired tricarboxylic acid cycle activity in mouse livers lacking cytosolic phosphoenolpyruvate carboxykinase. J Biol Chem 279(47): 48941-48949.
7. Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Mates JM, DeBerardinis RJ. 2011. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci USA 108(21): 8674-8679.
8. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. 2008. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452(7184): 181-186.
9. Dean JT, Tran L, Beaven S, Tontonoz P, Reue K, Dipple KM, Liao JC. 2009. Resistance to diet-induced obesity in mice with synthetic glyoxylate shunt. Cell Metab 9(6): 525-536.
10. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. 2007. Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104(49): 19345-19350.
11. Deshpande R, Yang TH, Heinzle E. 2009. Towards a metabolic and isotopic steady state in CHO batch cultures for reliable isotope-based metabolic profiling. Biotechnol J 4(2): 247-263.
12. Dorai H, Kyung YS, Ellis D, Kinney C, Lin C, Jan D, Moore G, Betenbaugh MJ. 2009. Expression of anti-apoptosis genes alters lactate metabolism of Chinese hamster ovary cells in culture. Biotechnol Bioeng 103(3): 592-608.
13. 13C mass isotopomer distributions for natural stable isotope abundance. J Mass Spectrom 31(3): 255-262.
14. Gagnon M, Hiller G, Luan YT, Kittredge A, DeFelice J, Drapeau D. 2011. High-end pH-controlled delivery of glucose effectively suppresses lactate accumulation in CHO fed-batch cultures. Biotechnol Bioeng 108(6): 1328-1337.
15. 13C, 1H] COSY NMR spectroscopy. Metab Eng 12(2): 138-149.
16. Goudar C, Biener R, Piret J, Konstantinov K. 2007. Metabolic flux estimation in mammalian cell cultures. Methods Biotechnol 24: 301-317.
17. Hakimi P, Yang J, Casadesus G, Massillon D, Tolentino-Silva F, Nye CK, Cabrera ME, Hagen DR, Utter CB, Baghdy Y, Johnson DH, Wilson DL, Kirwan JP, Kalhan SC, Hanson RW. 2007. Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J Biol Chem 282(45): 32844-32855.
18. Hassell T, Gleave S, Butler M. 1991. Growth inhibition in animal cell culture. The effect of lactate and ammonia. Appl Biochem Biotechnol 30(1): 29-41.
19. Hitosugi T, Kang S, Vander Heiden MG, Chung TW, Elf S, Lythgoe K, Dong S, Lonial S, Wang X, Chen GZ, Xie J, Gu TL, Polakiewicz RD, Roesel JL, Boggon TJ, Khuri FR, Gilliland DG, Cantley LC, Kaufman J, Chen J. 2009. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2(97): ra73. DOI: 10.1126/scisignal.2000431.
20. Huang YM, Hu W, Rustandi E, Chang K, Yusuf-Makagiansar H, Ryll T. 2010. Maximizing productivity of CHO cell-based fed-batch culture using chemically defined media conditions and typical manufacturing equipment. Biotechnol Prog 26(5): 1400-1410.
21. 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(4): 238-246.
22. Irish JM, Kotecha N, Nolan GP. 2006. Mapping normal and cancer cell signalling networks: Towards single-cell proteomics. Nat Rev Cancer 6(2): 146-155.
23. Kashif Sheikh JF, Lars KNielsen. 2005. Modeling hybridoma cell metabolism using a generic genome-scale metabolic model of Mus musculus. Biotechnol Prog 21: 112-121.
24. Kim SH, Lee GM. 2007. Functional expression of human pyruvate carboxylase for reduced lactic acid formation of Chinese hamster ovary cells (DG44). Appl Microbiol Biotechnol 76(3): 659-665.
25. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV. 2012. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 15(1): 110-121.
26. 13C2]glucose. Am J Physiol 274(5 Pt 1): E843-E851.
27. Li J, Wong CL, Vijayasankaran N, Hudson T, Amanullah A. 2012. Feeding lactate for CHO cell culture processes: Impact on culture metabolism and performance. Biotechnol Bioeng 109(5): 1173-1186.
28. Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP. 2010. Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res 70(15): 6368-6376.
29. Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M. 2007. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27(45): 12255-12266.
30. Noguchi Y, Young JD, Aleman JO, Hansen ME, Kelleher JK, Stephanopoulos G. 2009. Effect of anaplerotic fluxes and amino acid availability on hepatic lipoapoptosis. J Biol Chem 284(48): 33425-33436.
31. Pascoe DE, Arnott D, Papoutsakis ET, Miller WM, Andersen DC. 2007. Proteome analysis of antibody-producing CHO cell lines with different metabolic profiles. Biotechnol Bioeng 98(2): 391-410.
32. Rasmussen B, Davis R, Thomas J, Reddy P. 1998. Isolation, characterization and recombinant protein expression in Veggie-CHO: A serum-free CHO host cell line. Cytotechnology 28(1-3): 31-42.
33. Sengupta N, Rose ST, Morgan JA. 2011. Metabolic flux analysis of CHO cell metabolism in the late non-growth phase. Biotechnol Bioeng 108(1): 82-92.
34. She P, Shiota M, Shelton KD, Chalkley R, Postic C, Magnuson MA. 2000. Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism. Mol Cell Biol 20(17): 6508-6517.
35. Templeton N, Dean J, Reddy P, Young J. 2012. Oxidative TCA cycle metabolism is associated with peak antibody production in an industrial fed-batch CHO cell culture. Biotechnol Bioeng (in press).
36. Tserng KY, Gilfillan CA, Kalhan SC. 1984. Determination of carbon-13 labeled lactate in blood by gas chromatography/mass spectrometry. Anal Chem 56(3): 517-523.
37. Warburg O. 1956. On the origin of cancer cells. Science 123(3191): 309-314.
38. Wurm FM. 2004. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22(11): 1393-1398.
39. Young JD, Shastri AA, Stephanopoulos G, Morgan JA. 2011. Mapping photoautotrophic metabolism with isotopically nonstationary (13)C flux analysis. Metab Eng 13(6): 656-665.
40. Zamorano F, Wouwer AV, Bastin G. 2010. A detailed metabolic flux analysis of an underdetermined network of CHO cells. J Biotechnol 150(4): 497-508.
41. Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, et al. 2010. Regulation of cellular metabolism by protein lysine acetylation. Science 327(5968): 1000-1004.