Skip to main content

Expression of Foreign Genes in the yeast Pichia pastoris

  • Chapter
Genetic Engineering: Principles and Methods

Part of the book series: Genetic Engineering ((GEPM,volume 23))

Conclusion

Although the P. pastoris expression system is not suitable for the production of all foreign proteins, many are compatible with the system. For these proteins, there are major advantages to production in this yeast. Relative to higher eukaryotic expression systems, culturing costs are lower, yields (foreign protein/L of culture medium) are usually higher, and for secreted proteins, the initial purity of the product in the culture medium is higher. Relative to bacterial expression systems, the chances of recovering a eukaryotic foreign protein in its biologically active form are significantly higher with P. pastoris. Although few major P. pastoris- produced human Pharmaceuticals are on the market, several are in the clinical trial pipeline, including the anti-tumor drugs angiostatin and endostatin (44). In addition, P. pastoris is one of the only lower eukaryotic expression systems that is available to academic researchers as a complete kit (see Invitrogen catalog). Recent improvements in the system, including new marker host combinations and alternative promoters, should increase the range of proteins that can be produced by this methylotrophic host. As more proteins are successfully (or unsuccessfully) synthesized in P. pastoris, parameters involved with the optimal expression of specific classes of proteins will become better defined.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lin Cereghino, J. and Cregg, J.M. (2000) FEMS Micro. Rev. 24,45–66.

    Google Scholar 

  2. Higgins D.R. and Cregg, J.M. (eds.) (1998) Pichia Protocols, Humana Press, Totowa, N.J.

    Google Scholar 

  3. Wegner, G. (1990) FEMS Microbiol. Rev. 87, 279–284.

    Google Scholar 

  4. Veenhuis, M., van Dijken, J.P. and Harder, W. (1983) Adv. Microb. Physiol. 24, 1–82.

    PubMed  CAS  Google Scholar 

  5. Egli, T., van Dijken, J.P., Veenhuis, M., Harder, W. and Fiechter, A. (1980) Arch. Microbiol. 124, 115–121.

    Article  CAS  Google Scholar 

  6. Roggenkamp, R., Janowicz, Z., Stanikowski, B. and Hollenberg, C.P. (1984) Mol. Gen. Genet. 194, 489–498.

    Article  PubMed  CAS  Google Scholar 

  7. Ellis, S.B., Brust, P.F., Koutz, P.J., Waters, A.F., Harpold, M.M. and Gingeras, T.R. (1985) Mol. Cell. Biol. 5, 1111–1121.

    PubMed  CAS  Google Scholar 

  8. Cregg, J.M., Madden, K.R., Barringer, K.J., Thill, G.P. and Stillman, C.A. (1989) Mol. Cell. Biol. 9, 1316–1323.

    PubMed  CAS  Google Scholar 

  9. Koutz, P., Davis, G.R., Stillman, C., Barringer, K., Cregg, J.M. and Thill, G. (1989) Yeast 5, 167–177.

    Article  PubMed  CAS  Google Scholar 

  10. Couderc, R. and Baratti, J. (1980) Agric. Biol. Chem. 44, 2279–2289.

    CAS  Google Scholar 

  11. Cregg, J.M. and Madden, K.R. (1988) Dev. Ind. Microbiol. 29, 33–41.

    CAS  Google Scholar 

  12. Cregg, J.M., Barringer, K.J., Hessler, A.Y. and Madden, K.R. (1984) Mol. Cell. Biol. 5, 3376–3385.

    Google Scholar 

  13. Cregg, J.M., Shen, S., Johnson, M. and Waterham, H. (1998) in Higgins, D.R. and Cregg, J.M. (eds.) Pichia Protocols, Humana Press, Totowa, N.J. 103, 17–26.

    Google Scholar 

  14. Cregg, J.M. and Madden, K.R. (1989) Mol. Gen. Genet. 219, 320–323.

    Article  PubMed  CAS  Google Scholar 

  15. Romanos, M.A., Scorer, C.A. and Clare, J.J. (1992) Yeast 8, 423–488.

    Article  PubMed  CAS  Google Scholar 

  16. Cregg, J.M., Tschopp, J.F., Stillman, C., Siegal, R., Akong, M., Craig, W.S., Buckholz, R.G., Madden, K.R., Kellaris, P.A., Davis, G.R., Smiley, B.L., Cruze, J., Torregrossa, R., Velicelebi, G. and Thill, G.P. (1987) Bio/Technology 5, 479–485.

    Article  CAS  Google Scholar 

  17. Tschopp, J.F., Brust, P.F., Cregg, J.M., Stillman, C.A. and Gingeras, T.R. (1987) Nucl. Acids Res. 15, 3859–3876.

    PubMed  CAS  Google Scholar 

  18. Tschopp, J.F., Sverlow, G., Kosson, R., Craig, W. and Grinna, L. (1987) Bio/Technology 5, 1305–1308.

    Article  CAS  Google Scholar 

  19. Cregg, J.M. and Russell, K.A. in Higgins, D.R. and Cregg, J.M. (eds.) (1998) Humana Press, Pichia Protocols, Totowa, N.J. 103, 27–40.

    Google Scholar 

  20. Scorer, C.A., Buckholz, R.G., Clare, J.J. and Romanos, M.A. (1993) Gene 136, 111–119.

    Article  PubMed  CAS  Google Scholar 

  21. Brierley, R.A. in Higgins, D.R. and Cregg, J.M., (eds.) (1998) Pichia Protocols, Humana Press, Totowa, N.J. 103, 149–177.

    Google Scholar 

  22. Stratton, J., Chiruvolu, V. and Meagher, M. in Higgins, D.R. and Cregg, J.M., eds. (1998) Pichia Protocols, Humana Press, Totowa, N.J. 103, 107–120.

    Google Scholar 

  23. Romanos, M., Scorer, C., Sreekrishna, K. and Clare, J. in Higgins, D.R. and Cregg, J.M., (eds.) (1998) Pichia Protocols, Humana Press, Totowa, N.J. 103, 55–72.

    Google Scholar 

  24. Barr, K.A., Hopkins, S.A. and Sreekrishna, K. (1992) Pharm. Eng. 12, 48–51.

    Google Scholar 

  25. Vedvick, T., Buckholtz, R.G., Engel, M., Urcan, M., Kinney, J., Provow, S., Siegel, R.S. and Thill, G.P.(1991) J. Ind. Microbiol. 7, 197–202.

    Article  PubMed  CAS  Google Scholar 

  26. Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T. and Kivirikko, K.I. (1997) EMBO J. 16, 6702–6712.

    Article  PubMed  CAS  Google Scholar 

  27. Sreekrishna, K., Nelles, L., Potenz, R., Craze, J., Mazzaferro, P., Fish, W., Fuke, M., Holden, K., Phelps, D., Wood, P. and Parker, K. (1989) Biochemistry 28, 4117–4125.

    Article  PubMed  CAS  Google Scholar 

  28. Thill, G.P., Davis, G.R., Stillman, C., Holtz, G., Brierly, R., Engel, M., Buckholtz, R., Kenney, J., Provow, S., Vedvick, T. and Siegel, R.S. in Heslot, H., Davies, J., Florent, J., Bobichon, L., Durand, G. and Penasse, L., (eds.) (1990) Sixth International Symposium on the Genetics of Microorganisms. Paris: Societé Francaise de Microbiologie, 2, 477–490.

    Google Scholar 

  29. Clare, J.J., Romanos, M.A., Rayment, F.B., Rowedder, J.E., Smith, M.A., Payne, M.M., Sreekrishna, K. and Henwood, C.A. (1991) Gene 105, 205–212.

    Article  PubMed  CAS  Google Scholar 

  30. Scorer, C.A., Clare, J.J., McCombie, W.R., Romanos, M.A. and Sreekrishna, K. (1993) Bio/Technology 12, 181–184.

    Google Scholar 

  31. Higgins, D.R., Busser, K., Comiskey, J., Whittier, P.S., Purcell, T.J. and Hoeffler, J.P. in Higgins, D.R. and Cregg, J.M., (eds.) (1998) Pichia Protocols, Humana Press, Totowa, N.J. 103, 41–53.

    Google Scholar 

  32. Chen, Y.L., Cino, L., White, C.E. and Komives, E.A. (1996) J. Chem. Technol. Biotechnol. 67, 143–148.

    Article  CAS  Google Scholar 

  33. Gleeson, M.A.G., White, C., Meininger, D.P. and Komives, E.A. in Higgins, D.R. and Cregg, J.M., (eds.) (1998) Pichia Protocols, Humana Press, Totowa, N.J. 103, 81–94.

    Google Scholar 

  34. Sreekrishna, K. in Baltz, R.H., Hegeman, G.D. and Skatrud, P.L., (eds.) (1993) Industrial Microorganisms: Basic and Applied Molecular Genetics. American Society of Microbiology, Washington, D.C. 119–126.

    Google Scholar 

  35. Waterham, H.R., Digan, M.E., Koutz, P.J., Lair, S.V. and Cregg, J.M. (1997) Gene 186, 37–44.

    Article  PubMed  CAS  Google Scholar 

  36. Schena, M., Picard, D. and Yamamoto, K.R. in Guthrie, C. and Fink, G. (eds.) (1991) Guide to Yeast Genetics and Molecular Biology. Academic Press, San Diego, CA. 194, 389–398.

    Google Scholar 

  37. Shen, S., Suiter, G., Jeffries, T.W. and Cregg, J.M. (1998) Gene 216, 93–102.

    Article  PubMed  CAS  Google Scholar 

  38. Liu, H., Tan, X., Russell, K.A., Veenhuis, M. and Cregg, J.M. (1995) J. Biol. Chem. 270, 10940–10951.

    PubMed  CAS  Google Scholar 

  39. Sears, I.B., O’Connor, J., Rossanese, O.W. and Glick B.S. (1998) Yeast 14, 783–790.

    Article  PubMed  CAS  Google Scholar 

  40. Trimble, R.B., Atkinson, P.H., Tschopp, J.F., Townsend, R.R. and Maley, F. (1991) J. Biol. Chem. 266, 22807–22817.

    PubMed  CAS  Google Scholar 

  41. Cregg, J.M. and Higgins, D.R. (1995) Can. J. Bot. 73(Suppl 1), S891–897.

    CAS  Google Scholar 

  42. Grinna, L.S. and Tschopp, J.F. (1989) Yeast 5, 107–115.

    Article  PubMed  CAS  Google Scholar 

  43. Lin Cereghino, G.P., Lin Cereghino, J., Sunga, A.J., Johnson, M.A., Lim, M., Gleeson, M.A.G. and Cregg, J.M. (2001) Gene (in press).

    Google Scholar 

  44. Sim, B.K., O’Reilly, M.S., Liang, H., Fortier, A.H., He, W., Madsen, J.W., Lapcevich, R. and Nacy, C.A. (1997) Cancer Res 57, 1329–1334.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic Publishers

About this chapter

Cite this chapter

Cereghino, G.P.L., Sunga, A.J., Cereghino, J.L., Cregg, J.M. (2002). Expression of Foreign Genes in the yeast Pichia pastoris. In: Setlow, J.K. (eds) Genetic Engineering: Principles and Methods. Genetic Engineering, vol 23. Springer, Boston, MA. https://doi.org/10.1007/0-306-47572-3_9

Download citation

  • DOI: https://doi.org/10.1007/0-306-47572-3_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46645-8

  • Online ISBN: 978-0-306-47572-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics