Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis

Bioprocess and Biosystems Engineering

Volumn 34, Issue 5, 2011, Pages 533-545

  Niklas, Jens ^a   Schräder, Eva ^b   Sandig, Volker ^c   Noll, Thomas ^b   Heinzle, Elmar ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b BIELEFELD UNIVERSITY   (Germany)

^c PROBIOGEN AG   (Germany)

Author keywords

Cell culture; Growth phases; Kinetics; Mammalian cell; Metabolic engineering; Production

Indexed keywords

BATCH CULTIVATION; CELL LINES; CELLULAR COMPONENTS; CELLULAR METABOLISM; COMPUTATIONAL EFFORT; DYNAMIC CHANGES; DYNAMIC DATA; ENERGY METABOLISM; ENERGY SPILLING; FED-BATCH PRODUCTION; FEEDING STRATEGIES; FLUX ESTIMATION; GROWTH PHASIS; HUMAN CELL LINES; MAIN EVENT; MAMMALIAN CELLS; MEDIA OPTIMIZATION; METABOLIC ENGINEERING; METABOLIC FLUX ANALYSIS; METABOLIC SHIFT; MICROTITER PLATES; OVERFLOW METABOLISM; PRODUCTION PROCESS; PYRUVATES; QUANTITATIVE CHARACTERIZATION; SPLINE FITTING; THERAPEUTIC PROTEIN; TIME-RESOLVED; WASTE PRODUCTION;

AMINO ACIDS; ANIMAL CELL CULTURE; BATCH CELL CULTURE; CELLS; ENERGY CONVERSION; GENETIC ENGINEERING; MAMMALS; PHYSIOLOGY;

METABOLISM;

ADENOSINE TRIPHOSPHATE; ASPARTATE AMINOTRANSFERASE; ASPARTATE AMMONIA LIGASE; ASPARTIC ACID; GLUTAMATE AMMONIA LIGASE; GLUTAMATE DEHYDROGENASE; GLUTAMIC ACID; GLUTAMINE; GLYCINE; GLYCINE HYDROXYMETHYLTRANSFERASE; OXALOACETIC ACID; PROLINE; PYRUVATE DEHYDROGENASE; PYRUVIC ACID; SERINE DEHYDRATASE;

AMINO ACID METABOLISM; ARTICLE; BIOENGINEERING; BIOREACTOR; BIOTRANSFORMATION; CELL CULTURE; CELL GROWTH; CELL METABOLISM; CELL STRAIN; CELL STRAIN AGE1 HN; CITRIC ACID CYCLE; CONTROLLED STUDY; CULTURE MEDIUM; ELECTRON TRANSPORT; ENERGY METABOLISM; ENZYME ACTIVITY; GLYCOLYSIS; HUMAN; HUMAN CELL; METABOLIC FLUX ANALYSIS; METABOLITE; MICROTITER PLATE ASSAY; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROCEDURES CONCERNING CELLS; PROCESS OPTIMIZATION;

BIOMASS; BIOREACTORS; BRAIN; CELL COUNT; CELL CULTURE TECHNIQUES; CELL LINE; CITRIC ACID CYCLE; CULTURE MEDIA; GLUCOSE; GLUTAMINE; GLYCOLYSIS; HUMANS; KINETICS; MODELS, BIOLOGICAL; PYRUVIC ACID;

MAMMALIA;

EID: 79956205237     PISSN: 16157591     EISSN: 16157605     Source Type: Journal    
DOI: 10.1007/s00449-010-0502-y     Document Type: Article

References (60)

1. PM O'Callaghan DC James 2008 Systems biotechnology of mammalian cell factories Brief Funct Genomic Proteomic 7 2 95 110 10.1093/bfgp/eln012 (Pubitemid 351728951)
2. N Ferrer-Miralles J Domingo-Espin JL Corchero E Vazquez A Villaverde 2009 Microbial factories for recombinant pharmaceuticals Microb Cell Fact 8 17 10.1186/1475-2859-8-17
3. FM Wurm 2004 Production of recombinant protein therapeutics in cultivated mammalian cells Nat Biotechnol 22 11 1393 1398 10.1038/nbt1026 1:CAS:528:DC%2BD2cXptlSls7k%3D (Pubitemid 39482858)
4. AK Pavlou JM Reichert 2004 Recombinant protein therapeutics-success rates, market trends, values to 2010 Nat Biotechnol 22 12 1513 1519 10.1038/nbt1204-1513 1:CAS:528:DC%2BD2cXhtVCku7%2FE (Pubitemid 40039448)
5. G Walsh 2006 Biopharmaceutical benchmarks 2006 Nat Biotechnol 24 7 769 776 10.1038/nbt0706-769 1:CAS:528:DC%2BD28XmvFaguro%3D (Pubitemid 44086612)
6. DM Dinnis DC James 2005 Engineering mammalian cell factories for improved recombinant monoclonal antibody production: lessons from nature? Biotechnol Bioeng 91 2 180 189 10.1002/bit.20499 1:CAS:528:DC%2BD2MXlvFGitL8%3D (Pubitemid 41158945)
7. Rose T, Winkler K, Brundke E, Jordan I, Sandig V (2005) Alternative strategies and new cell lines for high-level production of biopharmaceuticals. In: Modern biopharmaceuticals, Wiley-VCH, Germany, pp 761-777
8. Sandig V, Rose T, Winkler K, Brecht R (2005) Mammalian cells. In: Production of recombinant proteins. Wiley-VCH, Germany, pp 233-252
9. N Kumar P Gammell M Clynes 2007 Proliferation control strategies to improve productivity and survival during CHO based production culture : a summary of recent methods employed and the effects of proliferation control in product secreting CHO cell lines Cytotechnology 53 1-3 33 46 10.1007/s10616-007-9047-6 1:CAS:528:DC%2BD2sXmsFKjurg%3D (Pubitemid 46944867)
10. M al-Rubeai RP Singh 1998 Apoptosis in cell culture Curr Opin Biotechnol 9 2 152 156 10.1016/S0958-1669(98)80108-0 1:CAS:528:DyaK1cXjtFehtrs%3D (Pubitemid 28195000)
11. MB Fogolin R Wagner M Etcheverrigaray R Kratje 2004 Impact of temperature reduction and expression of yeast pyruvate carboxylase on hGM-CSF-producing CHO cells J Biotechnol 109 1-2 179 191 10.1016/j.jbiotec.2003.10.035 1:CAS:528:DC%2BD2cXivVKmsb8%3D (Pubitemid 38452583)
12. E Trummer K Fauland S Seidinger K Schriebl C Lattenmayer R Kunert K Vorauer-Uhl R Weik N Borth H Katinger D Muller 2006 Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors Biotechnol Bioeng 94 6 1033 1044 10.1002/bit.21013 1:CAS:528:DC%2BD28XnvF2lu7s%3D (Pubitemid 44221048)
13. SK Yoon JY Song GM Lee 2003 Effect of low culture temperature on specific productivity, transcription level, and heterogeneity of erythropoietin in Chinese hamster ovary cells Biotechnol Bioeng 82 3 289 298 10.1002/bit.10566 1:CAS:528:DC%2BD3sXivVSrs74%3D (Pubitemid 36402541)
14. HK Oh MK So J Yang HC Yoon JS Ahn JM Lee JT Kim JU Yoo TH Byun 2005 Effect of N-acetylcystein on butyrate-treated Chinese hamster ovary cells to improve the production of recombinant human interferon-β-1a Biotechnol Prog 21 4 1154 1164 10.1021/bp050057v 1:CAS:528:DC%2BD2MXlvVegsrk%3D (Pubitemid 41099586)
15. YH Sung YJ Song SW Lim JY Chung GM Lee 2004 Effect of sodium butyrate on the production, heterogeneity and biological activity of human thrombopoietin by recombinant Chinese hamster ovary cells J Biotechnol 112 3 323 335 10.1016/j.jbiotec.2004.05.003 1:CAS:528:DC%2BD2cXmslegtLY%3D (Pubitemid 39093964)
16. K Eyer A Oeggerli E Heinzle 1995 On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine Biotechnol Bioeng 45 1 54 62 10.1002/bit.260450108 1:CAS:528:DyaK2MXjsl2murg%3D
17. I Jordan A Vos S Beilfuss A Neubert S Breul V Sandig 2009 An avian cell line designed for production of highly attenuated viruses Vaccine 27 5 748 756 10.1016/j.vaccine.2008.11.066 1:CAS:528:DC%2BD1MXmvVOgsg%3D%3D
18. U Sauer 2006 Metabolic networks in motion: 13C-based flux analysis Mol Syst Biol 2 62 10.1038/msb4100109 (Pubitemid 46061084)
19. J Nielsen 2003 It is all about metabolic fluxes J Bacteriol 185 24 7031 7035 10.1128/JB.185.24.7031-7035.2003 1:CAS:528:DC%2BD3sXpvVaqs7k%3D (Pubitemid 37521234)
20. RR Balcarcel LM Clark 2003 Metabolic screening of mammalian cell cultures using well-plates Biotechnol Prog 19 1 98 108 10.1021/bp025617u 1:CAS:528:DC%2BD38XpsVSnsrk%3D (Pubitemid 36219309)
21. HP Bonarius V Hatzimanikatis KP Meesters CD de Gooijer G Schmid J Tramper 1996 Metabolic flux analysis of hybridoma cells in different culture media using mass balances Biotechnol Bioeng 50 3 299 318 10.1002/(SICI)1097- 0290(19960505)50:3<299::AID-BIT9>3.0.CO;2-B 1:CAS:528:DyaK28Xitleiur4%3D (Pubitemid 26116733)
22. J Niklas F Noor E Heinzle 2009 Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2 Toxicol Appl Pharmacol 240 3 327 336 10.1016/j.taap.2009.07.005 1:CAS:528:DC%2BD1MXht1GmtbzN
23. Y Sidorenko A Wahl M Dauner Y Genzel U Reichl 2008 Comparison of metabolic flux distributions for MDCK cell growth in glutamine- and pyruvate-containing media Biotechnol Prog 24 2 311 320 10.1021/bp0702673 1:CAS:528:DC%2BD1cXptlyktQ%3D%3D (Pubitemid 351520343)
24. A Wahl Y Sidorenko M Dauner Y Genzel U Reichl 2008 Metabolic flux model for an anchorage-dependent MDCK cell line: characteristic growth phases and minimum substrate consumption flux distribution Biotechnol Bioeng 101 1 135 152 10.1002/bit.21873 1:CAS:528:DC%2BD1cXpslKqt7k%3D
25. R Deshpande TH Yang E Heinzle 2009 Towards a metabolic and isotopic steady state in CHO batch cultures for reliable isotope-based metabolic profiling Biotechnol J 4 2 247 263 10.1002/biot.200800143 1:CAS:528: DC%2BD1MXjtl2ktbs%3D
26. C Altamirano A Illanes S Becerra JJ Cairo F Godia 2006 Considerations on the lactate consumption by CHO cells in the presence of galactose J Biotechnol 125 4 547 556 10.1016/j.jbiotec.2006.03.023 1:CAS:528:DC%2BD28XpsVWlsrc%3D (Pubitemid 44333124)
27. F Llaneras J Pico 2007 A procedure for the estimation over time of metabolic fluxes in scenarios where measurements are uncertain and/or insufficient BMC Bioinformatics 8 421 10.1186/1471-2105-8-421 (Pubitemid 351175220)
28. HP Bonarius A Ozemre B Timmerarends P Skrabal J Tramper G Schmid E Heinzle 2001 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 Biotechnol Bioeng 74 6 528 538 10.1002/bit.1145 1:CAS:528:DC%2BD3MXmsFKgtL8%3D (Pubitemid 32825468)
29. U Hofmann K Maier A Niebel G Vacun M Reuss K Mauch 2008 Identification of metabolic fluxes in hepatic cells from transient 13C-labeling experiments: part I experimental observations Biotechnol Bioeng 100 2 344 354 10.1002/bit.21747 1:CAS:528:DC%2BD1cXlslCktrc%3D (Pubitemid 351758176)
30. K Maier U Hofmann M Reuss K Mauch 2008 Identification of metabolic fluxes in hepatic cells from transient 13C-labeling experiments: part II. Flux estimation Biotechnol Bioeng 100 2 355 370 10.1002/bit.21746 1:CAS:528:DC%2BD1cXlslCkt74%3D (Pubitemid 351758177)
31. RR Deshpande E Heinzle 2009 Online monitoring of oxygen in spinner flasks Biotechnol Lett 31 5 665 669 10.1007/s10529-009-9919-2 1:CAS:528: DC%2BD1MXkt1yisLs%3D
32. JO Kromer M Fritz E Heinzle C Wittmann 2005 In vivo quantification of intracellular amino acids and intermediates of the methionine pathway in Corynebacterium glutamicum Anal Biochem 340 1 171 173 10.1016/j.ab.2005.01.027 (Pubitemid 40404113)
33. NC Duarte SA Becker N Jamshidi I Thiele ML Mo TD Vo R Srivas BO Palsson 2007 Global reconstruction of the human metabolic network based on genomic and bibliomic data Proc Natl Acad Sci USA 104 6 1777 1782 10.1073/pnas.0610772104 1:CAS:528:DC%2BD2sXitVaqu7w%3D (Pubitemid 46239855)
34. R Hyde PM Taylor HS Hundal 2003 Amino acid transporters: roles in amino acid sensing and signalling in animal cells Biochem J 373 Pt 1 1 18 10.1042/BJ20030405 1:CAS:528:DC%2BD3sXkvVentrg%3D (Pubitemid 36819495)
35. Berg JM, Tymoczko JL, Stryer L (2003) Biochemie, 5th edn. Spektrum Akademischer Verlag, Berlin
36. RS Kaplan 2001 Structure and function of mitochondrial anion transport proteins J Membr Biol 179 3 165 183 10.1007/s002320010046 1:CAS:528: DC%2BD3MXjt1OlsrY%3D (Pubitemid 32165794)
37. JM Savinell BO Palsson 1992 Network analysis of intermediary metabolism using linear optimization I. Development of mathematical formalism J Theor Biol 154 4 421 454 10.1016/S0022-5193(05)80161-4 1:CAS:528:DyaK38Xkt1elu7s%3D
38. KK Frame WS Hu 1990 Cell volume measurement as an estimation of mammalian cell biomass Biotechnol Bioeng 36 2 191 197 10.1002/bit.260360211 1:STN:280:DC%2BD1cvisFOhtg%3D%3D (Pubitemid 20331178)
39. LK Nielsen S Reid PF Greenfield 1997 Cell cycle model to describe animal cell size variation and lag between cell number and biomass dynamics Biotechnol Bioeng 56 4 372 379 10.1002/(SICI)1097-0290(19971120)56:4<372::AID-BIT3>3. 0.CO;2-L 1:CAS:528:DyaK2sXmsleqsr8%3D (Pubitemid 27468933)
40. SH Kim GM Lee 2007 Down-regulation of lactate dehydrogenase-A by siRNAs for reduced lactic acid formation of Chinese hamster ovary cells producing thrombopoietin Appl Microbiol Biotechnol 74 1 152 159 10.1007/s00253-006-0654-5 1:CAS:528:DC%2BD2sXhtVans7o%3D (Pubitemid 46183480)
41. A Gambhir R Korke J Lee PC Fu A Europa WS Hu 2003 Analysis of cellular metabolism of hybridoma cells at distinct physiological states J Biosci Bioeng 95 4 317 327 1:CAS:528:DC%2BD3sXkslChtrk%3D (Pubitemid 36570536)
42. Henry O, Jolicoeur M, Kamen A (2010) Unraveling the metabolism of HEK-293 cells using lactate isotopomer analysis. Bioprocess Biosyst Eng
43. J Modak WD Deckwer AP Zeng 2002 Metabolic control analysis of eucaryotic pyruvate dehydrogenase multienzyme complex Biotechnol Prog 18 6 1157 1169 10.1021/bp025613p 1:CAS:528:DC%2BD38XotF2lu7w%3D (Pubitemid 35450870)
44. AP Zeng J Modak WD Deckwer 2002 Nonlinear dynamics of eucaryotic pyruvate dehydrogenase multienzyme complex: decarboxylation rate, oscillations, and multiplicity Biotechnol Prog 18 6 1265 1276 10.1021/bp020097o 1:CAS:528:DC%2BD38XmvVGnsbw%3D (Pubitemid 35450884)
45. J Neermann R Wagner 1996 Comparative analysis of glucose and glutamine metabolism in transformed mammalian cell lines, insect and primary liver cells J Cell Physiol 166 1 152 169 10.1002/(SICI)1097-4652(199601)166:1<152::AID- JCP18>3.0.CO;2-H 1:CAS:528:DyaK28Xit1Cmuw%3D%3D (Pubitemid 26017790)
46. CB Elias E Carpentier Y Durocher L Bisson R Wagner A Kamen 2003 Improving glucose and glutamine metabolism of human HEK 293 and Trichoplusia ni insect cells engineered to express a cytosolic pyruvate carboxylase enzyme Biotechnol Prog 19 1 90 97 10.1021/bp025572x 1:CAS:528:DC%2BD38XpsFWmtL4%3D (Pubitemid 36219308)
47. N Irani M Wirth J van Den Heuvel R Wagner 1999 Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction Biotechnol Bioeng 66 4 238 246 10.1002/(SICI)1097- 0290(1999)66:4<238::AID-BIT5>3.0.CO;2-6 1:CAS:528:DyaK1MXotFalsr4%3D (Pubitemid 30016598)
48. C Paredes E Prats JJ Cairo F Azorin L Cornudella F Godia 1999 Modification of glucose and glutamine metabolism in hybridoma cells through metabolic engineering Cytotechnology 30 1-3 85 93 10.1023/A:1008012518961 1:CAS:528:DyaK1MXjsl2ksr4%3D (Pubitemid 29212108)
49. Y Genzel JB Ritter S Konig R Alt U Reichl 2005 Substitution of glutamine by pyruvate to reduce ammonia formation and growth inhibition of mammalian cells Biotechnol Prog 21 1 58 69 10.1021/bp049827d 1:CAS:528:DC%2BD2cXhtVegtLbP (Pubitemid 40218472)
50. T Omasa K Furuichi T Iemura Y Katakura M Kishimoto K Suga 2010 Enhanced antibody production following intermediate addition based on flux analysis in mammalian cell continuous culture Bioprocess Biosyst Eng 33 1 117 125 10.1007/s00449-009-0351-8 1:CAS:528:DC%2BD1MXhsFyjsLvJ
51. K Chen Q Liu L Xie PA Sharp DI Wang 2001 Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production Biotechnol Bioeng 72 1 55 61 10.1002/1097-0290(20010105)72:1<55::AID- BIT8>3.0.CO;2-4 1:CAS:528:DC%2BD3MXitVOktQ%3D%3D
52. JB Russell 2007 The energy spilling reactions of bacteria and other organisms J Mol Microbiol Biotechnol 13 1-3 1 11 10.1159/000103591 1:CAS:528:DC%2BD2sXovFygtr4%3D (Pubitemid 351368995)
53. L Xie DI Wang 1996 Material balance studies on animal cell metabolism using a stoichiometrically based reaction network Biotechnol Bioeng 52 5 579 590 10.1002/(SICI)1097-0290(19961205)52:5<579::AID-BIT5>3.0.CO;2-G 1:CAS:528:DyaK28Xms1Wqtrg%3D (Pubitemid 26376640)
54. J Niklas K Schneider E Heinzle 2010 Metabolic flux analysis in eukaryotes Curr Opin Biotechnol 21 1 63 69 10.1016/j.copbio.2010.01.011 1:CAS:528:DC%2BC3cXjslSjtbc%3D
55. LE Quek S Dietmair JO Kromer LK Nielsen 2010 Metabolic flux analysis in mammalian cell culture Metab Eng 12 2 161 171 10.1016/j.ymben.2009.09.002 1:CAS:528:DC%2BC3cXit1OmurY%3D
56. C Zupke G Stephanopoulos 1995 Intracellular flux analysis in hybridomas using mass balances and in vitro (13)C nmr Biotechnol Bioeng 45 4 292 303 10.1002/bit.260450403 1:CAS:528:DyaK2MXktVKns74%3D
57. HP Bonarius B Timmerarends CD de Gooijer J Tramper 1998 Metabolite-balancing techniques versus 13C tracer experiments to determine metabolic fluxes in hybridoma cells Biotechnol Bioeng 58 2-3 258 262 10.1002/(SICI)1097-0290(19980420)58:2/3<258::AID-BIT20>3.0.CO;2-7 1:CAS:528:DyaK1cXht12kt7s%3D (Pubitemid 28136385)
58. WN Lee LG Boros J Puigjaner S Bassilian S Lim M Cascante 1998 Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1, 2-13C2]glucose Am J Physiol 274 5 pt 1 E843 E851 1:CAS:528:DyaK1cXjsFSisbs%3D
59. VR Velagapudi C Wittmann K Schneider E Heinzle 2007 Metabolic flux screening of Saccharomyces cerevisiae single knockout strains on glucose and galactose supports elucidation of gene function J Biotechnol 132 4 395 404 10.1016/j.jbiotec.2007.08.043 1:CAS:528:DC%2BD2sXht12gtbrF (Pubitemid 350051081)
60. L Xie DI Wang 1994 Applications of improved stoichiometric model in medium design and fed-batch cultivation of animal cells in bioreactor Cytotechnology 15 1-3 17 29 10.1007/BF00762376 1:STN:280:DyaK2M3gtVOgtw%3D%3D