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Pichia pastoris

  • Koti Sreekrishna
  • Keith E. Kropp

Abstract

Interest in the study of nonconventional yeasts (yeasts other than Saccharomyces cerevisiae and Schizosaccharomyces pombe) has increased dramatically in the past few years (Reiser et al. 1990). One such category is methylotrophic yeasts (Wegner and Harder 1986; Harder et al. 1986), e.g., Pichia pastoris, Hansanula polymorpha, Candida boidinii, etc. Methylotrophic yeasts have the ability to use methanol as a sole source of carbon and energy. Adaptation to growth on methanol is associated with induction of methanol oxidase, MOX (also referred to as alcohol oxidase, AOX), dihydroxy acetone synthase DAS, and several other enzymes involved in methanol metabolism. The most spectacular increase, however, is seen with alcohol oxidase, which is virtually absent in glucose-grown cells, but can account for over 30% of the cell protein in methanol-grown cells. Extensive proliferation of peroxisomes, accounting for over 80% of the cell volume, is also observed in methanol-grown cells (Veenhuis et al. 1983). Due to these characteristics, methylotrophic yeasts have gained the attention of biochemists, molecular biologists, cell biologists, biotechnologists, microbiologists, and chemists in academics and industry.

Keywords

Human Serum Albumin Pichia Pastoris Alcohol Oxidase Methylotrophic Yeast AOXI Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Barnett JA, Payne RW, Yarrow D (1990) Yeasts. Characteristics and identification. Cambridge University Press, CambridgeGoogle Scholar
  2. Barr KA, Hopkins SA, Sreekrishna K (1992) Protocol for efficient secretion of HSA developed from Pichia pastoris. Pharm Eng 12: 48–51Google Scholar
  3. Basu M, Nettleton MY, Dharm E, Manning RF, Despreaux CW, Hakimi J, Kochan JP (1992) Purification and characterization of a soluble form of the human IgE-receptor (α-subunit) expressed in Pichia pastoris. American Society for Biochemistry and Molecular Biology/Biophysical Society Joint meeting, Abstr #1507, February 9–13, HoustonGoogle Scholar
  4. Becker DM, Guarente L (1992) Protocol for high efficiency yeast transformation In: Chang DC, Chassy BM, Saunders JA, Sowers AE (eds) Guide to electroporation and electrofusion Academic Press, New York, pp 501–505Google Scholar
  5. Brierley RA, Davis GR, Holtz GC, Gleeson MA, Howard BD (1992) Production of insulin-like growth factor-1 in methylotrophic yeast cells. International Patent Application, No WO 92/04363Google Scholar
  6. Buckholz RG, Brierley RE, Odiorne MS, Siegel RS, Wondrack LM (1991) CD4 production in Pichia pastoris. International Patent Application, No WO 91/05057Google Scholar
  7. Clare JJ, Rayment FB, Ballantine SP, Sreekrishna K, Romanos MA (1991a) High-level expression of tetanus toxin fragment C in Pichia pastoris strains containing multiple tandem integration of the gene. Bio/Technology 9: 455–460PubMedCrossRefGoogle Scholar
  8. Clare JJ, Romanos MA, Rayment FB, Rowedder JE, Smith MA, Payne MM, Sreekrishna K, Henwood CA (1991b) Production of mouse epidermal growth factor in yeast: high-level secretion using Pichia pastoris strains containing multiple gene copies. Gene 105: 205–212PubMedCrossRefGoogle Scholar
  9. Cregg JM, Madden KR (1988) Development of the methylotrophic yeast, Pichia pastoris as a host for the production of foreign proteins. Dev Ind Microbiol 29: 33–41Google Scholar
  10. Cregg JM, Barringer KJ, Hessler AY, Madden KR (1985) Pichia pastoris as a host system for transformations. Mol Cell Biol 5: 3376–3385PubMedGoogle Scholar
  11. Cregg JM, Tschopp JF, Stilman C, Siegel R, Akong M, Craig WS, Buckholz RG, Madden KR, Kellaris PA, Davis GR, Smiley BL, Cruze J, Toregrossa R, Velicelebi G, Thill GP (1987) High-level expression and efficient assembly of hepatitis B surface antigen in methylotrophic yeast, Pichia pastoris. Bio/Technology 5: 479–485CrossRefGoogle Scholar
  12. Cregg JM, Madden KR, Barringer KJ, Thill GP, Stilton CA (1989) Functional characterization of the two alcohol oxidase genes from the yeast Pichia pastoris. Mol Cell Biol 9: 1316–1323PubMedGoogle Scholar
  13. Cregg JM, Vedvick TS, Raschke WC (1993) Recent advances in the expression of foreign genes in Pichia pastoris. Bio/Technology 11: 905–910PubMedCrossRefGoogle Scholar
  14. Despreaux CW, Manning RF (1993) The dacA gene of Bacillus stearothermophilus coding for D-alanine carboxy peptidase: cloning, structure and expression in E. Coli and Pichia pastoris. Gene 131: 35–41PubMedCrossRefGoogle Scholar
  15. Digan ME (1990) Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase gene. European Patent Application, No 0374 913 AlGoogle Scholar
  16. Digan ME, Lair SV (1986) Genetic methods for the methylotrophic yeast, Pichia pastoris. In: von Borstel RC, Cooper TG (eds) Abstr 13th Int Conf on Yeast Genetics and Molecular Biology Yeast 2 (1986): S89 (Spec Issue)Google Scholar
  17. Dohmen JR, Strasser AWM, Honer CB, Hollenberg CP (1991) An efficient transformation procedure enabling long term storage of competent cells of various yeast genera. Yeast 7: 691–692PubMedCrossRefGoogle Scholar
  18. Ellis SB, Brust PF, Koutz PJ, Waters AF, Harpold MM, Gingeras TR (1985) Isolation of alcohol oxidase and two other methanol-regulatable genes from the yeast Pichia pastoris. Mol Cell Biol 5: 1111–1121PubMedGoogle Scholar
  19. Gould S J, McCollum D, Spong AP, Heyman JA, Subramani S (1992) Development of the yease Pichia pastoris as a model organism for genetic and molecular analysis of peroxisomal assembly. Yeast 8: 613–628PubMedCrossRefGoogle Scholar
  20. Grinna LS, Tschopp JF (1989) Size distribution and general structural features of N-linked oligosaccharides from the methylotrophic yeast Pichia pastoris. Yeast 5: 107–115PubMedCrossRefGoogle Scholar
  21. Guthrie C, Fink GR (eds) (1991) Guide to yeast genetics and molecular biology. Methods in Enzymology, vol 194. Academic Press, New YorkGoogle Scholar
  22. Hagenson MJ, Holden KA, Parker KA, Wood PJ, Cruze JA, Fuke M, Hopkins TR, Stroman DW (1989) Expression of streptokinase in Pichia pastoris yeast. Enzyme Microb Technol 11:650–656CrossRefGoogle Scholar
  23. Harder W, Trotsenko YA, Bystrykh LV, Egli T (1986) Microbial growth on C1 compounds. In: Van Verseveld HW, Duine JA (eds) Proceedings of the 5th International Symposium Martinus Nijhoff, Dordrecht, pp 138–157Google Scholar
  24. Hopkins TR (1991) Physical and chemical cell disruption for the recovery of intracellular proteins. In: Seetharam R, Sharma SK (eds) Purification and analysis of recombinant proteins Mercel Dekker, New York, pp 57–83Google Scholar
  25. Ito H, Fukuda Y, Murata K, Kimura A (1983) Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153: 161–168Google Scholar
  26. Kukuruzinska MA, Bergh MLE, Jackson BJ (1987) Protein glycosylation in yeast. Annu Rev Biochem 56: 915–944PubMedCrossRefGoogle Scholar
  27. Kurtzman CP (1984a) Pichia Hansen. In: Kreger-van Rij NJW (ed) The yeasts: a taxonomic study. Elsevier Amsterdam, pp 295–378Google Scholar
  28. Kurtzman CP (1984b) Synonomy of the yeast genera Hansenula and Pichia demonstrated through comparisons of the deoxyribonucleic acid relatedness. Antonie Leeuwenhoek 50: 209–217PubMedCrossRefGoogle Scholar
  29. Laroche Y, Storme V, Meutter JD, Messens J, Lauwerey SM (1994) High-level secretion and very efficient isotopic labelling of tick anti-coagulant peptide (TAP) expressed in the methylotrophic yeast, Pichia pastoris. Bio/Technology 12: 1119–1124PubMedCrossRefGoogle Scholar
  30. Liu H, Tan X, Veenhuis M, McCollum D, Cregg JM (1992) An efficient screen for peroxi-some-deficient mutants of Pichia pastoris. J Bacteriol 174: 4943–4951PubMedGoogle Scholar
  31. Reiser J, Glumoff V, Kalin M, Urs O (1990) Transfer and expression of heterologous genes in yeasts other than Saccharomyces cerevisiae. In: Fiechter A (ed) Advances in biochemical engineering/biotechnology, vol 43. Springer, Berlin Heidelberg New York, pp 76–97Google Scholar
  32. Rodringuez M, Rubiera R, Penichet M, Montesinos R, Cremata J, Falcon V, Sanchez G, Bringas R, Cordoves C, Valdes M, Lleonart R, Herrera L, dela Fuente J (1994) High level expression of the β microplus Bm86 antigen in the yeast Pichia-pastoris forming highly immunogenic particles for cattle. J Biotechnol 33: 135–146CrossRefGoogle Scholar
  33. Romanos MA, Clare JJ, Beesley KM, Rayment FB, Ballantine SP, Makoff AJ, Dougan G, Fairweather NF, Charles IG (1991) Recombinant Bordetella pertussis (P69) from the yeast Pichia pastoris: high-level production and immunological properties. Vaccine 9: 901–906PubMedCrossRefGoogle Scholar
  34. Romanos MA, Scorer CA, Clare JJ (1992) Foreign gene expression in yeast: a review. Yeast 8: 423–488PubMedCrossRefGoogle Scholar
  35. Rose MD, Winston F, Hieter P (1990) Methods in yeast genetics: a laboratory course manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New YorkGoogle Scholar
  36. Scorer CA, Buckholz RG, Sreekrishna K, Clare JJ, Romanos MA (1992) Expression of HIV gp120 in Pichia pastoris: selection for multi-copy transformants using drug resistance. 16th Int Conf on Yeast Genetics and Molecular Biology, Vienna, Austria, Topic No 14–49BGoogle Scholar
  37. Scorer CA, Clare JJ, McCombie WR, Romanos MA, Sreekrishna K (1994) Rapid selection using G418 of high copy number transformants of Pichia pastoris for high-level foreign gene expression. Bio/Technology 12: 181–184PubMedCrossRefGoogle Scholar
  38. Siegel RS, Buckholz RG, Thill GP, Wondrack LM (1990) Production of epidermal growth factor in methylortrophic yeasts. International Patent Application, No WO 90/10697Google Scholar
  39. Sreekrishna K (1993) Strategies for optimizing protein expression and secretion in the methylotrophic yeast Pichia pastoris. In: Baltz RH, Hegeman GD, Skatrud PL (eds) “Industrial microorganisms: basic and applied molecular genetics” American Society of Microbiology, Washington DC, pp 119–126Google Scholar
  40. Sreekrishna K, Prevatt WD, Thill GP, Davis GR, Koutz P, Barr KA, Hopkins SA (1993) Production of Bacillus entomotoxins in methylotrophic yeast. European Patent Application, Publication no. EP 0586 892 AlGoogle Scholar
  41. Sreekrishna K, Tschopp JF, Fuke M (1987) Invertase gene (SUC2) of Saccharomyces cerevisiae as a dominant marker for transformation of Pichia pastoris. Gene 59: 115–125PubMedCrossRefGoogle Scholar
  42. Sreekrishna K, McCombie WR, Potenz R, Parker KA, Mazzaferro PK, Maine GM, Lopez JL, Divelbiss DK, Holden KA, Barr RD, Fuke M (1988a) Clonal variation in the expression of human tumor necrosis factor (TNF) in the methylotrophic yeast Pichia pastoris, Presented at the 5th Annual Biotech USA Industry Conference and Exhibition, San FranciscoGoogle Scholar
  43. Sreekrishna K, Potenz R, Cruze JA, McCombie WR, Rarker KA, Nelles L, Mazzaferro PK, Holden KA, Harrison RG, Wood PJ, Phelps DA, Hubbard CE, Fuke M (1988b) High level expression of heterologous proteins in methylotrophic yeast Pichia pastoris. J Basic Microbil 28: 265–278CrossRefGoogle Scholar
  44. Sreekrishna K, Nelles L, Potenz R, Cruze J, Mazzaferro P, Fish W, Fuke M, Holden K, Phelps D, Wood P, Parker K (1989) High-level expression, purification, and characterization of recombinant human tumor necrosis factor synthesized in the methylotrophic yeast Pichia pastoris. Biochemistry 28: 4117–4125PubMedCrossRefGoogle Scholar
  45. Sreekrishna K, Barr KA, Hoard SA, Prevatt WD, Torregrosa RE, Levingston RE, Cruze JA, Wegner GH (1990) Expression of human serum albumin in Pichia pastoris. 15th Int Congr on Yeast Genetics and Molecular Biology, Hague, The Netherlands, Topic No 09–37BGoogle Scholar
  46. Thill GP, Davis GR, Stillman GR, Holtz C, Brierly R, Engel M, Buckholz R, Kinney J, Provo S, Vedvick T, Siegel RS (1990) Positive and negative effects of multi-copy integrated expression vectors on protein expression in Pichia pastoris. In: Proc 6th Int Symp on Genetic of Industrial Microorganisms, Strasbourg, pp 477–490Google Scholar
  47. Trimble RB, Atkinson PH, Tschopp JF, Townsend RR, Maley F (1991) Structure of oligosaccharides on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris. J Biol Chem 266: 22807–22817PubMedGoogle Scholar
  48. Tschopp JF, Svelow G, Kosson R, Craig W, Grinna L (1987) High-level secretion of glycosylated invertase in the methylotrophic yeast, Pichia pastoris. Bio/Technology 5: 1305–1308CrossRefGoogle Scholar
  49. Veenhuis M, van Dijken JP, Harder W (1983) The significance of peroxisomes in the metabolism of one-carbon compounds in yeasts. Adv Microb Physiol 24: 1–82PubMedCrossRefGoogle Scholar
  50. Wagner SL, Siegel RS, Vedvick TS, Raschke WC, van Nostrand WE (1992) High-level expression, purification and characterization of the Kunitz-type protease inhibitor domain of protease nexin-2/amyloid β-protein precursor. Biochem Biophys Res Commun 186: 1138–1145PubMedCrossRefGoogle Scholar
  51. Wegner GH (1983) Biochemical conversions by yeast fermentation at high cell densities. US Patent 4: 329,414Google Scholar
  52. Wegner GH (1990) Emerging applications of the methylotrophic yeasts. FEMS Microb Rev 87: 279–284CrossRefGoogle Scholar
  53. Wegner GH, Harder W (1986) Methylotrophic yeasts-1986. Microbial growth on C1 compounds. In: Van Verseveld HW, Duine JA (eds) Proc 5th Int Symp Martinus Nijhoff Publishers, Dordrecht, pp 139–149Google Scholar
  54. Yamada M, Azuma T, Matsuba T, Iida H, Suzuki H, Yamamoto K, Kohli Y, Hori H (1994) Secretion of human intracellular aspartic proteinase Cathepsine expressed in the methylotrophic yeast, Pichia pastoris and characterization of produced recombinant cathepsine. Bichom Biophy Acta 1206: 279–285CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • Koti Sreekrishna
    • 1
  • Keith E. Kropp
    • 1
  1. 1.Hoechst Marion Roussel Inc.CincinnatiUSA

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