Plant Cells pp 127-156 | Cite as

The Production of Foreign Proteins from Genetically Modified Plant Cells

  • Eddie James
  • James M. Lee
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 72)


While traditionally used to produce natural products, plant suspension cultures can also be utilized for the production of foreign proteins. Production of these high-value products in plant cells is an economically viable alternative to other systems, particularly in cases where the protein must be biologically active. There are several advantages to using plant cells for the large-scale production of secreted proteins. Plant cell media are composed of simple sugars and salts and are therefore less expensive and complex than mammalian media. Consequently, purification of secreted protein is simpler and more economical. Additionally, plant cell derived proteins are likely to be safer than those derived from other systems, since plant cell pathogens are not harmful to humans. In this chapter, we will review foreign protein production from plant cells. To begin, we will discuss the behavior of plant cell cultures, products produced by plant cells, protein secretion and its relationship to purification, and the performance of plant cells as compared to whole plants and other alternative hosts. After a brief discussion of gene transfer techniques, we will present strategies to overcome the limitations of protein production, including protein stabilization, novel production schemes, modeling, and scale-up considerations. To conclude, we will discuss implications for future development of this technology.


Plant cell Foreign protein Transgenic Secretion Increased production 


  1. 1.
    Tabata M, Fujita Y (1985) In: Zaitlin M, Day P, Hollaender A (eds) Biotechnology in plant sciences. Academic Press, San Diego, p 207Google Scholar
  2. 2.
    Remi Shih NJ, McDonald KA, Dandekar AM, Girbes T, Iglesias R, Jackman AP (1998) Plant Cell Rep 17:531CrossRefGoogle Scholar
  3. 3.
    Lee J (1992) Biochemical engineering. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
  4. 4.
    An G (1985) Plant Physiol 79:568CrossRefGoogle Scholar
  5. 5.
    Kusnadi AR, Nikolov ZL, Howard JA (1997) Biotechnol Bioeng 56:473CrossRefGoogle Scholar
  6. 6.
    Magnuson NS, Linzmaier PM, Gao J, Reeves R, An G, Lee JM (1996) Protein Exp Purif 7:220CrossRefGoogle Scholar
  7. 7.
    Glick BR, Pasternak JJ (1994) Molecular biotechnology: principles and applications of recombinant DNA. ASM Press, Washington, DCGoogle Scholar
  8. 8.
    Liu F, Lee JM (1999) Biotech Bioproc Eng 4:259CrossRefGoogle Scholar
  9. 9.
    Matsumoto S, Ikura K, Ueda M, Sasaki R (1995) Plant Mol Biol 27:1163CrossRefGoogle Scholar
  10. 10.
    Magnuson NS, Linzmaier PM, Reeves R, An G, HayGlass K, Lee JM (1998) Protein Exp Purif 13:45CrossRefGoogle Scholar
  11. 11.
    Wongsamuth R, Doran PM (1997) Biotechnol Bioeng 54:401CrossRefGoogle Scholar
  12. 12.
    James E, Wang C, Wang Z, Reeves R, Shin JH, Magnuson NS, Lee JM (2000) Protein Exp Purif 19:131CrossRefGoogle Scholar
  13. 13.
    Fischer R, Liao YC, Drossard J (1999) J Immunol Methods 226:1CrossRefGoogle Scholar
  14. 14.
    Firek S, Draper J, Owen MRL, Gandecha A, Cockburn B, Whitelam GC (1993) Plant Mol Biol 23:861CrossRefGoogle Scholar
  15. 15.
    Hogue RS, Lee JM, An G (1990) Enzyme Microb Technol 12:533CrossRefGoogle Scholar
  16. 16.
    Tagge EP, Chandler J, Harris B, Czako M, Marton L, Willingham MC, Burbage C, Afrin L, Frankel AE (1996) Protein Exp Purif 8:109CrossRefGoogle Scholar
  17. 17.
    Terashima M, Murai Y, Kawamura M, Nakanishi S, Stoltz T, Chen L, Drohan W, Rodriguez RL, Katoh S (1999) Appl Microbiol Biotechnol 52:516CrossRefGoogle Scholar
  18. 18.
    Jones R, Robinson D (1989) New Phytologist 111:567CrossRefGoogle Scholar
  19. 19.
    Lund P, Dunsmuir P (1992) Plant Mol Biol 18:47CrossRefGoogle Scholar
  20. 20.
    Denecke J, Botterman J, Deblaere R (1990) The Plant Cell 2:51CrossRefGoogle Scholar
  21. 21.
    Ma JKC, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T (1995) Science 268:716CrossRefGoogle Scholar
  22. 22.
    Carpita N, Sabularse D, Montezinos D, Helmer DP (1979) Science 205:1144CrossRefGoogle Scholar
  23. 23.
    Brodelius P, Nilsson K (1983) Eur J Appl Microbiol Biotechnol 17:275CrossRefGoogle Scholar
  24. 24.
    Fraley RT, Rogers SG, Horsch RB, Sanders PR, Flick JS, Adams SP, Bittner ML, Brand LA, Fink CL, Fry JS (1983) Proc Natl Acad Sci USA 80:4803CrossRefGoogle Scholar
  25. 25.
    Hiatt A, Cafferkey R, Bowdish K (1989) Nature (London) 342:76CrossRefGoogle Scholar
  26. 26.
    Baez J, Russell D (2000) ACS National Meeting. San Francisco, CaliforniaGoogle Scholar
  27. 27.
    Rodriguez RL, Lonnerdal B, Nandi S, Wu L, Huang J, Huang N (2000) ACS National Meeting. San Francisco, CaliforniaGoogle Scholar
  28. 28.
    Nikolov Z, Kusnadi A, Woodard S, Azzoni A, Miranda E (2000) ACS National Meeting. San Francisco, CaliforniaGoogle Scholar
  29. 29.
    Mason HS, Tacket CO, Richter LJ, Arntzen CJ (1998) Res Immunol 149:71CrossRefGoogle Scholar
  30. 30.
    Fischer R, Drossard J, Commandeur U, Schillberg S, Emans N (1999) Biotechnol Appl Biochem 30:101Google Scholar
  31. 31.
    Conrad U, Fiedler U (1994) Plant Mol Biol 26:1023CrossRefGoogle Scholar
  32. 32.
    Trudel J, Potvin C, Asselin A (1995) Plant Sci 106:55CrossRefGoogle Scholar
  33. 33.
    Fischer R, Emans N, Schuster F, Hellwig S, Drossard J (1999) Biotechnol Appl Biochem 30:109Google Scholar
  34. 34.
    Sehnke PC, Pedrosa L, Paul AL, Frankel AE, Ferl RJ (1994) J Biol Chem 269:22473Google Scholar
  35. 35.
    Birch RG (1997) Annu Rev Plant Physiol Plant Mol Biol 48:297CrossRefGoogle Scholar
  36. 36.
    Gao J, Lee JM, An G (1991) Plant Cell Rep 10:553CrossRefGoogle Scholar
  37. 37.
    Hadi MZ, McMullen MD, Finer JJ (1996) Plant Cell Rep 15:500CrossRefGoogle Scholar
  38. 38.
    Potrykus I (1990) Ciba Found Symp 1990 154:198Google Scholar
  39. 39.
    Rhodes CA, Pierce DA, Mettler IJ, Mascarenhas D, Detmer JJ (1988) Science 240:204CrossRefGoogle Scholar
  40. 40.
    Laursen CM, Krzyzek RA, Flick CE, Anderson PC, Spencer TM (1994) Plant Mol Biol 24:51CrossRefGoogle Scholar
  41. 41.
    Joersbo M, Okkels FT (1996) Plant Cell Rep 16:219CrossRefGoogle Scholar
  42. 42.
    Wang AS, Evans RA, Altendorf PR, Hanten JA, Doyle MC, Rosichan JL (2000) Plant Cell Rep 19:654CrossRefGoogle Scholar
  43. 43.
    Elliott AR, Campbell JA, Dugale B, Brettell RIS, Grof CPL (1999) Plant Cell Rep 18:707CrossRefGoogle Scholar
  44. 44.
    Allen GC, Hall G Jr, Michalowski S, Newman W, Steven S, Weissinger AK, Thompson WF (1996) Plant Cell 8:899CrossRefGoogle Scholar
  45. 45.
    Wahl MF, An G, Lee JM (1995) Biotech Lett 17:463CrossRefGoogle Scholar
  46. 46.
    Ryland JR, Linzmaier PM, Lee JM (2000) J Microbiol Biotech 10:449CrossRefGoogle Scholar
  47. 47.
    LaCount W, An G, Lee JM (1997) Biotech Lett 19:93CrossRefGoogle Scholar
  48. 48.
    Sharp J, Doran PM (1999) Biotechnol Bioprocess Eng 4:253CrossRefGoogle Scholar
  49. 49.
    Bateman KS, Congiu M, Tregear GW, Clarke AE, Anderson MA (1997) Biotechnol Bioeng 53:226CrossRefGoogle Scholar
  50. 50.
    Chavan AJ, Haley BE, Volkin DB, Marfia KE, Verticelli AM, Bruner MW, Draper JP, Burke CJ, Middaugh CR (1994) Biochemistry 33:7193CrossRefGoogle Scholar
  51. 51.
    Vuillard L, Madern D, Franzetti B, Rabilloud R (1995) Anal Biochem 230:290CrossRefGoogle Scholar
  52. 52.
    Xie G, Timasheff SN (1997) Protein Sci 6:211CrossRefGoogle Scholar
  53. 53.
    Schena M, Lloyd AM, Davis RW (1991) Proc Natl Acad Sci USA 88:10421CrossRefGoogle Scholar
  54. 54.
    Van der Zaal EJ, Droog FNJ, Boot CJM, Hensgens LAM, Hoge JHC, Schilperoort RA, Libbenga KR (1991) Plant Mol Biol 16:983CrossRefGoogle Scholar
  55. 55.
    Yoshida K, Kasai T, Garcia MRC, Sawada S, Shoji T, Shimizu S, Yamazaki K, Komeda Y, Shinmyo A (1995) Appl Microbiol Biotechnol. 44:466CrossRefGoogle Scholar
  56. 56.
    Mett VL, Lochhead LP, Reynolds PHS (1993) Proc Natl Acad Sci USA 90:4567CrossRefGoogle Scholar
  57. 57.
    Gatz C, Kaiser A, Wendenburg GR (1991) Mol Gen Genet 227:229CrossRefGoogle Scholar
  58. 58.
    Claes B, Smalle J, Dekeyser R, Van Montagu M, Caplan A (1991) Plant J 1:15CrossRefGoogle Scholar
  59. 59.
    Chan MT, Chao YC, Yu SM (1994) J Biol Chem 269:17635Google Scholar
  60. 60.
    Caddick MX, Greenland AJ, Jepson I, Krause KP, Qu N, Riddell KV, Salter MG, Schuch W, Sonnewald U, Tomsett AB (1998) Nat Biotechnol 16:177CrossRefGoogle Scholar
  61. 61.
    Boetti H, Chevalier L, Denmat LA, Thomas D, Thomasset B (1999) Biotechnol Bioeng 64:1CrossRefGoogle Scholar
  62. 62.
    James E (2001) Ph.D Thesis, Washington State UniversityGoogle Scholar
  63. 63.
    Fischer R, Vaquero-Martin C, Sack M, Drossard J, Emans N, Commandeur U (1999) Biotechnol Appl Biochem 30:113Google Scholar
  64. 64.
    Gal S, Pisan B, Hohn T, Grimsley N, Hohn B (1992) Virology 187:525CrossRefGoogle Scholar
  65. 65.
    Shen WH, Hohn B (1995) J Gen Virol 76:965CrossRefGoogle Scholar
  66. 66.
    Scholthof HB, Scholthof KG, Jackson AO (1996) Annu Rev Phytopathol 34:299CrossRefGoogle Scholar
  67. 67.
    Frazier GC, White WK, Dougall DK (1989) Biotechnol Bioeng 33:313CrossRefGoogle Scholar
  68. 68.
    Linzmaier PM (1998) PhD thesis, Washington State UniversityGoogle Scholar
  69. 69.
    Hooker BS, Lee JM, An G (1990) Biotechnol Bioeng 35:296CrossRefGoogle Scholar
  70. 70.
    Li GQ, Shin JH, Lee JM (1995) Biotech Techniques 9:715CrossRefGoogle Scholar
  71. 71.
    Curtis WR, Emery AH (1993) Biotechnol Bioeng 42:520CrossRefGoogle Scholar
  72. 72.
    Bohme C, Schröder MB, Jung-Heiliger H, Lehmann J (1997) Appl Microbiol Biotechnol 48:149CrossRefGoogle Scholar
  73. 73.
    Sahai O, Knuth M (1985) Biotechnol Prog 1:1Google Scholar
  74. 74.
    Schmidt AJ, Lee JM, An G (1989) Biotech Bioeng 33:1437CrossRefGoogle Scholar
  75. 75.
    Nilsson K, Brodelius P, Mosbach K (1987) Methods Enzymol 135:222CrossRefGoogle Scholar
  76. 76.
    Bodeutsch T, James E, Lee JM (1999) AIChE National Meeting. Dallas, TexasGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • Eddie James
    • 1
  • James M. Lee
    • 1
  1. 1.Department of Chemical EngineeringWashington State University PullmanWashingtonUSA

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