Fermentation Strategies for Recombinant Protein Expression in the Methylotrophic Yeast Pichia pastoris

  • Zhang, Senhui (Biological Process Development Facility, Department of Chemical Engineering, University) ;
  • Inan, Mehmet (Biological Process Development Facility, Department of Chemical Engineering, University) ;
  • Meagher, Michael M. (Biological Process Development Facility, Department of Chemical Engineering, University)
  • Published : 2000.07.01

Abstract

Fermentation strategies for recombinant protein production in Pichia pastoris have been investigated and are reviewed here. Characteristics of the expression system, such as phenotypes and carbon utilization, are summarized. Recently reported results such as growth model establishment, app58lication of a methanol sensor, optimization of substrate feeding strategy, DOstat controller design, mixed feed technology, and perfusion and continuous culture are discussed in detail.

Keywords

References

  1. Pichia pastoris. Biotechnology v.5 High-level expression and efficient assembly of hepatitis B surface antigen in the methylotrophic yeast, Cregg, J. M.;J. F. Tschopp;C. Stillman;R. Siegel;M. Akong;W. S. Craig;R. G. Buckholz;K. R. Madden;A. Kellaris;G. R. Davis;B. L. Smiley;J. Cruze;R. Torregrossa;G. Velicelebi;G. P. Thill
  2. Yeast v.8 For-eign gene expression in yeast: a review. Romanos, M. A.;C. A. Scorer;J. J. Clare
  3. Biotechnology v.11 Re-cent advances in the expression of foreign genes in Pichia pastoris. Cregg, J. M.;T. S. Vedvick;W. C. Raschke
  4. Bio-logical Research on Industrial Yeast. v.2 Development of yeast transformation systems and construction of methanol-utilization-defective mutants of Pichia pastoris by gene disruption. Cregg, J. M.;K. R. Madden
  5. Ann. NY Acad. Sci. v.589 Fermentation development of recombi-nant Pichia pastoris expressing the heterologous gene: bo-vine lysozyme. Brierley, R. A.;C. Bussineau;R. Kosson;A. Melton;R. S. Siegel
  6. Mol. Cell Biol. v.9 Functional characterization of the two alcohol oxidase genes from the yeast Pichia pas-toris. Cregg, J. M.;K. R. Madden;K. J. Barringer;G. P. Thill;C. A. Stillman
  7. Enzyme Microb. Technol. v.21 Recombinant protein production in an alcohol oxidase-defective strain of Pichia pastoris in fed-batch fermenta-tions. Chiruvolu, V.;J. M. Cregg;M. M. Meagher
  8. Methods Mol. Biol. v.103 Generation of protease-deficient strains and their use in heterologous protein expression. Gleeson, M. A.;C. E. White;D. P. Meininger;E. A. Komives
  9. Bio-technology v.12 High-level secretion and very efficient isotopic labeling of tick anticoagulant peptide (TAP) ex-pressed in the methylotrophic yeast, Pichia pastoris. Laroche, Y.;V. Storme;J. De Meutter;J. Messens;M. Lauwereys
  10. Biotechnology v.9 High-level expression of teta-nus toxin fragment C in Pichia pastoris strains containing multiple tandem integrations of the gene. Clare, J. J.;F. B. Rayment;S. P. Ballantine;K. Sreekrishna;M. A. Romanos
  11. Agric. Biol. Chem. v.33 A yeast capable of utilizing methanol. Ogata, K.;H. Nishikawa;M. Ohsugi
  12. Metabolic regulation in methylotrophic yeasts. Micro-bial growth on C1 compounds. Proceedings of the 5th in-ternational symposium on microbial growth on C1com- pounds. Harder, W.;Y. A. Trotsenko;L. V. Bystrykh;T. Egli
  13. J. Basic. Microbiol. v.28 Genetic control of methanol utilization in yeasts. Sibirny, A. A.;V. I. Titorenko;M. V. Gonchar;V. M. Ubi-yvovk;G. P. Ksheminskaya;O. P. Vitvitskaya
  14. Adv. Microb. Physiol. v.24 The significance of peroxisomes in the metabolism of one-carbon compounds in yeasts. Veenhuis, M.;J. P. Van Dijken;W. Harder
  15. Yeast v.4 The methylotro-phic yeasts. Gleeson, M. A.;P. E. Sudbery
  16. Arch. Microbiol. v.156 Methanol and ethanol utiliza-tion in methylotrophic yeast Pichia pinus wild-type and mutant strains. Sibirny, A. A.;V. I. Titorenko;G. E. Teslyar;V. I. Petrushko;M. M. Kucher
  17. Eur. J. Biochem. v.5 Glycerol metabolism in yeasts. Pathways of utilization and pro-duction. Gancedo, C.;J. M. Gancedo;A. Sols
  18. Yeast v.3 Multilicity of mechanisms of carbon catabolite repression involved in the synthesis of alcohol oxidase in the methylotrophic yeast Pichia pinus. Sibirnyi, A. A., V. I. Titorenko, B. D. Efremov, and I. Tol-storukov
  19. Arch. Microbiol. v.124 Methanol metabolism in yeasts : Regula-tion of the synthesis of catabolic enzymes. Egli, T.;J. P. v. Dijken;M. Veenhuis;W. Harder;A. Fiechter
  20. Mol. Cell Biol. v.5 Isolation of alcohol oxidase and two other methanol regulatable genes from the yeast Pichia pastoris. Ellis, S. B.;P. F. Brust;P. J. Koutz;A. F. Waters;M. M. Harpold;T. R. Gingeras
  21. Mol. Gen. Genet. v.194 Biosynthesis and regulation of the peroxisomal methanol oxidase from the methylotrophic yeast Hansenula polymorpha. Roggenkamp, R.;Z. Janowicz;B. Stanikowski;C. P. Hollenberg
  22. J. Cell Sci. v.108 Divergent modes of auto-phagy in the methylotrophic yeast Pichia pastoris. Tuttle, D.;W. Dunn
  23. Appl. Biochem. Biotechnol. v.75 Effects of glycerol concentration and pH on growth of recombinant Pichia pastoris. Chiruvolu, V.;K. M. Eskridge;J. M. Cregg;M. M. Meagher
  24. Nu-cleic Acids Res. v.15 Expression of the lacZ gene from two methanol-regulated promoters in Pichia pastoris. Tschopp, J. F.;P. F. Brust;J. M. Cregg;C. A. Stillman;T. R. Gingeras
  25. Process Biochem. v.34 A novel feeding strategy for enhanced protein production by fed-batch fermentation in recombinant Pichia pastoris. Chauhan, A. K.;D. Arora;N. Khanna
  26. Gene v.190 Strategies for optimal synthesis and secretion of heterologous pro-teins in the methylotrophic yeast Pichia pastoris. Sreekrishna, K.;R. G. Brankamp;K. E. Kropp;D. T. Blankenship;J. T. Tsay;P. L. Smith;J. D. Wierschke;A. Subramaniam;L. A. Birkenberger
  27. Yeast v.14 A versatile set of vectors for constitutive and regu-lated gene expression in Pichia pastoris. Sears, I. B.;J. O'Connor;O. W. Rossanese;B. S. Glick
  28. Enzyme Microb. Technol. v.24 Opti-mization of temperature-glycerol-pH conditions for a fed-batch fermentation process for recombinant hook-worm (Ancylostoma caninum) anticoagulant peptide (AcAP-5) production by Pichia pastoris. Inan, M.;V. Chiruvolu;K. M. Eskridge;G. P. Vlasuk;K. Dickerson;S. Brown;M. M. Meagher
  29. US Patent 4,414,329 Biochemical conversions by yeast fermentation at high cell densities. Wegner, E. H.
  30. WO Patent 90/03431 Mixed feed recombinant yeast fermentation. Brierley, R. A.;R. S. Siegel;C. M. Bussineau;W. S. Craig;G. C. Holtz;G. R. Davis;R. G. Buckholz;G. P. Thill;L. M. Wondrack;M. E. Digan;M. M. Harpold;S. V. Lair;S. B. Ellis;M. E. Williams
  31. US Patent 5,324,639. Pro-duction of insulin-like growth factor-1 in methylotrophic yeast cells. Brierley, R. A.;G. R. Davis;G. C. Holtz
  32. WO Patent 90/10697 Production of epidermal growth factor in methylotrophic yeast cells. Siegel, R. S.;R. G. Buckholz;G. P. Thill;L. M. Won-drack
  33. Pichia Fermentation Process Guidelines. Invitrogen Co.
  34. Methods Mol. Biol. v.103 High cell-density fermentation. Stratton, J.;V. Chiruvolu;M. Meagher
  35. Biotechnol. Prog. v.12 Phosphate glass as a phosphate source in high cell density Escher-ichia coli fermentations. Curless, C.;J. Baclaski;R. Sachdev
  36. Current topics in gene expression annual meeting. High cell density fermentation of Pichia pastoris using non-phosphate precipitate forming sodium hexametaphos-phate as a phosphate source. Oehler, R.; G. Lesnicki;M. Galleno
  37. Biotechnol. Bioeng. v.34 Methylotrophic yeast Pichia pastoris produced in high-cell-density fer-mentations with high cell yields as vehicle for recombi-nant protein production. Siegel, R. S.;R. A. Brierley
  38. J. Gen. Microbiol. v.123 Theoretical analysis of media used in the growth of yeasts on methanol. Egli, T.;A. Fiechter
  39. Methods Mol. Biol. v.103 Secretion of recombinant human insulin-like growth factor I (IGF-I). Brierley, R. A.
  40. Biotechnol Bioeng v.70 Modeling Pichia pastoris growth on methanol and optimizing the production of a recombi-nant protein, the heavy-chain fragment C of botulinum neurotoxin, serotype A. Zhang, W.;M. A. Bevins;B. A. Plantz;L. A. Smith;M. M. Meagher
  41. Bio-technol. Bioeng. v.56 On-line monitoring and control of methanol con-centration in shake-flask cultures of Pichia pastoris. Guarna, M. M.;G. J. Lesnicki;B. M. Tam;J. Robinson;C. Z. Radziminski;D. Hasenwinkle;A. Boraston;E. Jervis;R. T. A. Macgillivray;R. F. B. Turner;D. G. Kilburn
  42. J. Ferm. Bioeng. v.86 Effect of methanol concentration on the production of human β2-glyco-protein I domain V by a recombinant Pichia pastoris: A simple system for the control of methanol concentration using a semiconductor gas sensor. Katakura, Y.;W. Zhang;G. Zhuang;T. Omasa;M. Kishi-moto;Y. Goto;K. Suga
  43. Advances in bio-chemical engineering/biotechnology. v.46 Optimization and control in fed-batch bioreactors. Shioya, S.;A. Fiechter (ed.)
  44. Ad-vances in Biochemical Engineering/Biotechnology. v.30 Fed-batch techniques in microbial process. Yamane, T.;S. Shimizu;A. Fiechter (ed.)
  45. Advances in Biochemical Engineering/Biotechnology. v.32 Modeling, optimiza-tion and control of semi-batch bioreactors. Parulekar, S. J.;H. C. Lim
  46. Annual Report of ICBiotech. International Center for Biotechnology Effect of methanol concentration on produc-tion of human β2-glycoprotein I domain V by a recombi-nant Pichia pastoris. Zhang, W.;Y. Katakura;T. Omasa;M. Kishimoto;K. Suga
  47. Biotechnol. Bioeng. v.63 Use of an ethanol sensor for feedback control of growth and expression of TBV25H in Saccha-romyces cerevisiae. Noronha, S. B.;L. W. Wagner;N. H. Matheson;J. Shiloach
  48. Biotechnol. Bioeng. v.68 Design of metabolic feed controllers: application to high-density fermentations of Pichia pas-toris. Chung, J. D.
  49. Biotechnol. Lett. v.22 Mixed-feed expo-nential feeding for fed-batch culture of recombinant me-thylotrophic yeast. Anjou, M. C.;A. J. Daugulis
  50. J. Ferment. Biotechnol. v.86 High-level expression of the methanol-inducible beta-galactosidase gene by perfusion culture of recombi-nant Pichia pastoris using a shaken ceramic membrane flask. Ohashi, R.;E. Mochizuki;Y. Kamoshita;T. Suzuki
  51. J. Chem. Technol. Biotechnol. v.67 Continuous production of thrombo-modulin from a Pichia pastoris fermentation. Chen, Y.;J. Krol;J. Cino;D. Freedman;C. White;E. Komives
  52. Biotechnology v.7 Continuous production of a novel lysozyme via secretion from the yeast, Pichia pastoris. Digan, M. E.;S. V. Lair;R. A. Brierley;R. S. Siegel;M. E. Williams;S. B. Ellis;P. A. Kellaris;S. A. Provow;W. S. Craig;G. Velicelebi;M. M. Harpold;G. P. Thill
  53. J. Biomol. NMR. v.13 Production of large quantities of isotopically labeled protein in Pichia pastoris by fermentation. Wood, M. J.;E. A. Komives
  54. Gene v.105 Production of mouse epidermal growth factor in yeast: high-level secretion using Pichia pastoris strains containing multiple gene copies. Clare, J. J.;M. A. Romanos;F. B. Rayment;J. E. Rowedder;M. A. Smith;M. M. Payne;K. Sreekrishna;C. A. Henwood
  55. Protein Expr. Purif. v.13 Pro-duction and purification of the heavy-chain fragment C of botulinum neurotoxin, serotype B, expressed in the methylotrophic yeast Pichia pastoris. Potter, K. J.;M. A. Bevins;E. V. Vassilieva;V. R. Chiruvolu;T. Smith;L. A. Smith;M. M. Meagher
  56. J. Biosci. Bioeng. v.89 High-level expression of recombinant human serum albumin from the methylotrophic yeast Pichia pastoris with minimal protease production and activation. Kobayashi, K.;S. Kuwae;T. Ohya;T. Ohda;M. Ohyama;H. Ohi;K. Tomomitsu;T. Ohmura
  57. Gene v.186 Isolation of the Pichia pastoris glyceral-dehyde-3-phosphate dehydrogenase gene and regulation and use of its promoter. Waterham, H. R.;M. E. Digan;P. J. Koutz;S. V. Lair;J. M. Cregg
  58. Gene v.216 A strong nitrogen source-regulated promoter for controlled expression of foreign genes in the yeast Pichia pastoris. Shen, S.;G. Sulter;T. W. Jeffries;J. M. Cregg