Comparative metabolite analysis to understand lactate metabolism shift in Chinese hamster ovary cell culture process

Biotechnology and Bioengineering

Volumn 109, Issue 1, 2012, Pages 146-156

  Luo, Jun ^a   Vijayasankaran, Natarajan ^a   Autsen, Jennifer ^a   Santuray, Rodell ^a   Hudson, Terry ^a   Amanullah, Ashraf ^a   Li, Feng ^a  

^a GENENTECH INC   (United States)

Author keywords

CHO cell culture; Copper; Fed batch; Lactate; Metabolomics; Oxidative pathway

Indexed keywords

ACETYL-COA; ANTIBODY PRODUCTION; CELL LINES; CELL PELLETS; CHINESE HAMSTER OVARY CELLS; COPPER CONCENTRATION; ENERGY METABOLISM; FED BATCHES; FREE FATTY ACID; GLYCOLYTIC INTERMEDIATE; LACTATE; MEDIA COMPONENTS; METABOLIC ANALYSIS; METABOLIC CAPACITIES; METABOLIC CHARACTERISTICS; METABOLIC PROFILES; METABOLIC SHIFT; METABOLITE ANALYSIS; METABOLITE PROFILES; METABOLOMICS; OVERFLOW METABOLISM; OXIDATIVE PATHWAYS; PROCESS PERFORMANCE; PYRUVATES; SINGLE CELLS; TCA CYCLE; TIME INTERVAL;

CELLS; COPPER; ENERGY EFFICIENCY; FATTY ACIDS; GLUCOSE; METABOLISM; METABOLITES; PATHOLOGY; PHOSPHOLIPIDS; PHYSIOLOGY;

CELL CULTURE;

ACETYL COENZYME A; ADENOSINE TRIPHOSPHATE; LACTIC ACID; PYRUVIC ACID;

ANIMAL CELL; ANIMAL CELL CULTURE; ANTIBODY PRODUCTION; ARTICLE; CELL GROWTH; CHEMICAL PARAMETERS; CHEMICALLY DEFINED MEDIUM; CHO CELL; CONTROLLED STUDY; CULTURE MEDIUM; GLYCOLYSIS; LACTATE CONSUMPTION; LACTATE METABOLISM; METABOLIC SHIFT; METABOLISM; METABOLITE; NONHUMAN; PHENOTYPE; SUPERNATANT;

ADENOSINE TRIPHOSPHATE; ANIMALS; CHO CELLS; COPPER; CRICETINAE; CRICETULUS; CULTURE MEDIA; ENERGY METABOLISM; FATTY ACIDS; GLUCOSE; LACTIC ACID; METABOLOME; PHOSPHOLIPIDS;

CRICETULUS GRISEUS;

EID: 81455141232     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.23291     Document Type: Article

References (39)

1. Altamirano C, Paredes C, Illanes A, Cairó JJ, Gòdia F. 2004. Strategies for fed-batch cultivation of t-PA producing CHO cells: Substitution of glucose and glutamine and rational design of culture medium. J Biotechnol 110(2): 171-179.
2. Borth N, Kral G, Katinger H. 1993. Rhodamine 123 fluorescence of immortal hybridoma cell lines as a function of glucose concentration. Cytometry 14(1): 70-73.
3. Brownlee M. 2001. Biochemistry and molecular cell biology of diabetic complications. Nature 414: 813-820.
4. Chen K, Liu Q, Xie L, Sharp PA, Wang DIC. 2000. Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production. Biotechnol Bioeng 72(1): 55-61.
5. 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.
6. Fiehn O. 2002. Metabolomics - the link between genotypes and phenotypes. Plant Mol Biol 48: 155-171.
7. Ford DA. 2002. Alterations in myocardial lipid metabolism during myocardial ischemia and reperfusion. Prog Lipid Res 41(1): 6-26.
8. Gagnon M, Hiller G, Luan Y-T, 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.
9. Glacken MW, Fleischaker RJ, Sinskey AJ. 1986. Reduction of waste product excretion via nutrient control: Possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells. Biotechnol Bioeng 28(9): 1376-1389.
10. Greiner EF, Guppy M, Brand K. 1994. Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J Biol Chem 269(50): 31484-31490.
11. Gybina AA, Prohaska JR. 2008. Copper deficiency results in amp-activated protein kinase activation and acetylcoa carboxylase phosphorylation in rat cerebellum. Brain Res 14(1204): 69-76.
12. Hinterkörner G, Brugger G, Müller D, Hesse F, Kunert R, Katinger H, Borth N. 2007. Improvement of the energy metabolism of recombinant cho cells by cell sorting for reduced mitochondrial membrane potential. J Biotechnol 129(4): 651-657.
13. Hoogeveen RCAM, Reaves SK, Reid PM, Reid BL, Lei KY. 1994. Copper deficiency shifts energy substrate utilization from carbohydrate to fat and reduces fat mass in rats. J Nutr 124(9): 1660-1666.
14. Jeffery J, Jornvall H. 1983. Enzyme relationships in a sorbitol pathway that bypasses glycolysis and pentose phosphates in glucose metabolism. Proc Natl Acad Sci USA 80(4): 901-905.
15. Kelly WA, Kesterson JW, Carlton WW. 1974. Myocardial lesions in the offspring of female rats fed a copper dificient diet. Exp Mol Pathol 20(1): 40-56.
16. 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: 659-665.
17. Korke R, Gatti Mde L, Lau A, Lim J, Seow T, Chung M, Hu W. 2004. Large scale gene expression profiling of metabolic shift of mammalian cells in culture. J Biotechnol 107(1): 1-17.
18. Lawton K, Berger A, Mitchell M, Milgram K, Evans A, Guo L, Hanson R, Kalhan S, Ryals J, Milburn M. 2008. Analysis of the adult human plasma metabolome. Pharmacogenomics 9(4): 383-397.
19. Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP. 2003. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem 278(10): 8516-8525.
20. Li F, Vijayasankaran N, Shen AY, Kiss R, Amanullah A. 2010. Cell culture processes for monoclonal antibody production. mAbs 2(5): 466-479.
21. Ma N, Ellet J, Okediadi C, Hermes P, McCormick E, Casnocha S. 2009. A single nutrient feed supports both chemically defined NS0 and CHO fed-batch processes: Improved productivity and lactate metabolism. Biotechnol Prog 25(5): 1353-1363.
22. Miller WM, Wilke CR, Blanch HW. 1988. Transient responses of hybridoma cells to lactate and ammonia pulse and step changes in continuous culture. Bioproc Biosyst Eng 3(3): 113-122.
23. Moore A, Mercer J, Dutina G, Donahue CJ, Bauer KD, Mather JP, Etcheverry T, Ryll T. 1997. Effects of temperature shift on cell cycle, apoptosis and nucleotide pools in CHO cell batch cultures. Cytotechnology 23(1-3): 47-54.
24. Neely J, Rovetto M, Whitmer J. 1976. Rate-limiting steps of carbohydrate and fatty acid metabolism in ischemic hearts. Acta Med Scand Suppl 587: 9-15.
25. Neuhofer W, Beck F-X. 2005. Response of renal medullary cells to osmotic stress. Contrib Nephrol 148: 21-34.
26. 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.
27. Passarella S, Bari Ld, Valenti D, Pizzuto R, Paventi G, Atlante A. 2008. Mitochondria and l-lactate metabolism. FEBS Lett 582(25-26): 3569-3576.
28. Qian Y, Khattak SF, Xing Z, He A, Kayne PS, Qian N-X, Pan S-H, Li ZJ. 2011. Cell culture and gene transcription effects of copper sulfate on cho cells. Biotechnol Prog 27(4): 1190-1194.
29. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. 2004. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 64: 985-993.
30. Seow TK, Korke R, Liang RCMY, Ong S-E, Ou K, Wong K, Hu W-S, Chung MCM. 2001. Proteomic investigation of metabolic shift in mammalian cell culture. Biotechnol Prog 17(6): 1137-1144.
31. Shen AY, Van de Goor J, Zheng L, Reyes AE, Krummen LA. 2006. Recombinant DNA technology and cell line development. In: Ozturk SS, Hu W-S, editors. Cell culture technology for pharmaceutical and cell-based therapies. Boca Raton, FL: CRC Press Taylor & Francis Group.
32. Tainer JA, Getzoff ED, Richardson JS, Richardson DC. 1983. Structure and mechanism of copper, zinc superoxide dismutase. Nature 206(5940): 284-287.
33. Tomlinson DR, Gardiner NJ. 2008. Glucose neurotoxicity. Nat Rev Neurosci 9(1): 36-45.
34. Urlaub G, Chasin LA. 1980. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci USA 77(7): 4216-4220.
35. Valenti D, Bari Ld, Atlante A, Passarella S. 2002. L-lactate transport into rat heart mitochondria and reconstruction of the l-lactate/pyruvate shuttle. Biochem J 364(Pt1): 101-104.
36. Vijayasankaran N, Shawley R, Yang Y, Shiratori M, Jamison K, Varma S, Caffaleatte C, Brooks D, Meier S, Zhang B, Gawlitzek M, Kiss R. Effect of copper on metabolism and productivity of industrial chinese hamster ovary cell cultures. Biotechnol Prog Submitted.
37. Xie L, Wang DIC. 1994. Fed-batch cultivation of animal cells using different medium design concepts and feeding strategies. Biotechnol Bioeng 43(11): 1175-1189.
38. Zeng H, Saari JT, Johnson WT. 2007. Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart. J Nutr 137(1): 14-18.
39. Zhou M, Crawford Y, Ng D, Tung J, Pynn AFJ, Meier A, Yuk IH, Vijayasankaran N, Leach K, Joly J, Snedecor B, Shen A. 2011. Decreasing lactate level and increasing antibody production in Chinese Hamster Ovary cells (CHO) by reducing the expression of lactate dehydrogenase and pyruvate dehydrogenase kinases. J Biotechnol 153: 27-34.