Metabolic shifts do not influence the glycosylation patterns of a recombinant fusion protein expressed in BHK cells

Biotechnology and Bioengineering

Volumn 69, Issue 2, 2000, Pages 129-139

  Cruz, Helder J ^a   Peixoto, Cristina M ^a   Nimtz, Manfred ^b   Alves, Paula M ^a   Dias, Elsa M ^a   Moreira, José L ^a   Carrondo, Manuel J T ^a,c  

^a Inst Biol Exp Tecnologica I   (Portugal)

^b HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^c UNIVERSIDADE NOVA DE LISBOA   (Portugal)

Author keywords

BHK 21 cells; Fusion protein; Glucose; Glutamine metabolism; Metabolic shifts; N linked oligosaccharide structures; Tumor targeted therapy

Indexed keywords

COMPOSITION EFFECTS; CONTINUOUS CELL CULTURE; GLUCOSE; METABOLISM; MOLECULAR STRUCTURE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHOSPHATES;

ADENOSINE TRIPHOSPHATE; GALACTOSE; HYDRAZINOLYSIS; METABOLIC SHIFTS; OLIGOSACCHARIDES;

PROTEINS;

HYBRID PROTEIN; IMMUNOGLOBULIN G; INTERLEUKIN 2;

AMINO ACID ANALYSIS; AMINO ACID METABOLISM; ARTICLE; CARBOHYDRATE ANALYSIS; CELL METABOLISM; CELL STRAIN BHK; NONHUMAN; PHOSPHORUS NUCLEAR MAGNETIC RESONANCE; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN METABOLISM; STRUCTURE ANALYSIS;

EID: 0034691774     PISSN: 00063592     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1097-0290(20000720)69:2<129::aid-bit2>3.0.co;2-5     Document Type: Article

References (37)

1. Burger C, Carrondo MJ, Cruz H, Cuffe M, Dias E, Griffiths JB, Hayes K, Hauser H, Looby D, Mielke C, Moreira JL, Rieke E, Savage AV, Stacey GN, Welge T. 1999. An integrated strategy for the process development of a recombinant antibody-cytokine fusion protein expressed in BHK cells. Appl Microbiol Biotechnol 52:345-353.
2. Conradt HS, Geyer R, Hoppe J, Grotjahn L, Plessing A, Mohr H. 1985. Structures of the major carbohydrates of natural human interleukin-2. Eur J Biochem 153:255-261.
3. -, and Chinese hamster ovary cells. J Biol Chem 264: 7368-17373.
4. Costa J, Grabenhorst E, Nimtz M, Conradt HS. 1997. Stable expression of the Golgi form and secretory variants of human fucosyltransferase III from BHK-21 cells. J Biol Chem 272:11613-11621.
5. Cruz HJ, Moreira JL, Stacey G, Dias EM, Hayes K, Looby D, Griffiths B, Carrondo MJT. 1998. Adaptation of BHK cells producing a recombinant protein to serum-free media and protein-free medium. Cytotechnol 26:59-64.
6. Cruz HJ, Ferreira AS, Freitas CM, Moreira JL, Carrondo MJT. 1999a. Metabolic responses to different glucose and glutamine levels in BHK cell culture. Appl Microbiol Biotechnol 51:579-585.
7. Cruz HJ, Moreira JL, Carrondo MJT. 1999b. Metabolic shifts by nutrient manipulation in continuous cultures of BHK cells. Biotechnol Bioeng 66:104-113.
8. Dirks W, Wirth M, Hauser H. 1993. Dicistronic transcription units for gene expression in mammalian cells. Gene 128:247-249.
9. Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. 1988. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem 263: 17755-17762.
10. Gawlitzek M, Valley U, Nimtz M, Wagner R, Conradt HS. 1995. Characterization of changes in the glycosylation pattern of recombinant proteins from BHK-21 cells due to different culture conditions. J Biotechnol 42:117-131.
11. Gawlitzek M, Valley U, Wagner R. 1998. Ammonium ion and glucosamine dependent increases of oligosaccharide complexity in recombinant glycoproteins secreted from cultivated BHK-21 cells. Biotechnol Bioeng 57:518-528.
12. Grabenhorst E, Hoffmann A, Nimtz M, Zettlmeissl G, Conradt HS. 1995. Construction of stable BHK-21 cells coexpresing human secretory glycoproteins and human Gal(β1-4)GlcNAc-R α2,6-sialyltransferase. α2,6-Linked NeuAc is preferentially attached to the Gal(ßl-4)GlcNAc(β1-2)Man(α1-3)-branch of diantennary oligosaccharides from secreted recombinant β-trace protein. Eur J Biochem 232: 718-725.
13. Grabenhorst E, Schlenke P, Pohl S, Nimtz M, Conradt HS. 1999. Genetic engineering of recombinant glycoproteins and the glycosylation pathway in mammalian host cells. Glycocon J 16:81-97.
14. Hakomori S. 1964. A rapid permethylation of glycolipid, and polysaccharide catalyzed by methylsulfinyl carbanion in dimethyl sulfoxide. J Biochem (Tokyo) 55:205-207.
15. Kunkel JP, Jan DCH, Jamieson JC, Butler M. 1998. Dissolved oxygen concentration in serum-free continuous culture affects N-linked glycosylation of a monoclonal antibody. J Biotechnol 62:55-71.
16. Laemmli UK. 1970. Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227:680-685.
17. Lifely MR, Hale C, Boyce S, Keen MJ, Phillips J. 1995. Glycosylation and biological activity of CAMPATH-1H expressed in different cell lines and grown under different culture conditions. Glycobiol 5:813-822.
18. Looby D, Moreira J, Stacey G, Cruz HJ, Cuffe M, Dias E, Hayes K, House H, Beardmore M, Savage A, Carrondo MJT, Griffiths JB. 1997. Alternative strategies for the production of an antibody-cytokine fusion protein from recombinant BHK cells. In: Carrondo MJT, Griffiths JB, Moreira JLP, editors. Animal cell technology. Dordrecht, The Netherlands: Kluwer Academic Publishers, p 797-800.
19. Lund J, Takahashi N, Hindley S, Tyler R, Goodall M, Jefferis R. 1993. Glycosylation of human IgG subclass and mouse IgG2b heavy chains secreted by mouse J558L transfectoma cell lines as chimeric antibodies. Hum Antibod Hybridomas 4:20-25.
20. Lund J, Takahashi N, Pound JD, Tyler R, Goodall M, Nakagawa H, Jefferis R. 1995. Oligosaccharide-protein interactions in IgG can modulate recognition by Fcγ receptors. FASEB J 9:115-119.
21. Lundberg P, Harmsen E, Ho C, Vogel HJ. 1990. Nuclear magnetic resonance studies of cellular metabolism. Anal Biochem 191:193-222.
22. Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB. 1995. Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-hinding protein. Nat Med 1:237-243.
23. Moreira JL, Cruz PE, Santana PC, Feliciano AS, Lehmann J, Carrondo MJT. 1995. Influence of power input and aeration method on mass transfer in a laboratory animal cell culture vessel. J Chem Tech Biotechnol 62:118-131.
24. Nimtz M, Noll G, Paques EP, Conradl HS. 1990. Carbohydrate structures of a human tissue plasminogen activator variant expressed in recombinant Chinese hamster ovary cells. FEBS Lett 271:14-18.
25. Nimtz M, Martin W, Wray V, Kloppel KD, Augustin J, Conradt HS. 1993. Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells. Eur J Biochem 213:39-56.
26. Nimtz M, Grabenhorst E, Gambert U, Costa J, Wray V, Morr M, Thiem J, Conradt HS. 1998. In vitro alphal-3 or alphal-4 fucosylation of type I and II oligosaccharides with secreted forms of recombinant human fucosyltransferases III and VI. Glycoconj J 15:873-883.
27. Nyberg GB, Balcarcel RR, Follstad BD, Stephanopoulos G, Wang DIC. 1999. Metabolic effects on recombinant interferon-γ glycosylation in continuous culture of chinese hamster ovary cells. Biotechnol Bioeng 62:336-347.
28. Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth D, Rademacher TW, Mizuochi T, Taniguchi T, Matsuta K, Takeuchi F, Nagano Y, Miyamoto T, Kobata A. 1985. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316:452-457.
29. Patel TP, Parekh RB, Moellering BJ, Prior CP. 1992. Different culture methods lead to differences in glycosylation of a murine IgG monoclonal antibody. Biochem J 285:839-845.
30. Robinson DK, Seamans TC, Gould SL, DiStefano DJ, Chan CP, Lee DK, Bibila T, Glazomitsky K, Munshi S, Daughterly B., et al. 1994. Optimization of a Fed-batch process for production of a recombinant antibody. Ann NY Acad Sci 745:285-296.
31. Routier FH, Davies MJ, Bergemann K, Hounsell EF. 1997. The glycosylation pattern of a humanized IgGI antibody (D1.3) expressed in CHO cells. Glycoconj J 14:201-207.
32. Santos H, Turner DL. 1986. Characterization of the improved sensitivity obtained using a flow method for oxygenation and mixing cell suspensions in NMR. J Magn Res 65:345-349.
33. Takahashi N, Ishii I, Ishihara H, Mori M, Tejima S, Jefferis R, Endo S, Arata Y. 1987. Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. Biochem 26:1137-1144.
34. von Hoegen I, Hofman U, Jaggle C-J, Strimatter W, Stadtmuller J, Matzku S. 1993. Immunoconjugates EP/24.12.93/EP93120865.
35. Wright A, Morrison SL. 1994. Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin Gl. J Exp Med 180:1087-1096.
36. Wright A, Morrison SL. 1997. Effect of glycosylation on antibody function: Implications for genetic engineering. Trends Biotechnol 15: 26-32.
37. Youings A, Chang S-C, Dwek RA, Scragg IG. 1996. Site-specific glycosylation of human immunoglobulin G is altered in four rheumatoid arthritis patients. Biochem 314:621-630.