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Pichia pastoris: A Recombinant Microfactory for Antibodies and Human Membrane Proteins

  • Goncalves, A.M. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior) ;
  • Pedro, A.Q. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior) ;
  • Maia, C. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior) ;
  • Sousa, F. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior) ;
  • Queiroz, J.A. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior) ;
  • Passarinha, L.A. (CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior)
  • Received : 2012.10.23
  • Accepted : 2012.12.22
  • Published : 2013.05.28

Abstract

During the last few decades, it has become evident that the compatibility of the yeast biochemical environment with the ability to process and translate the RNA transcript, along with its capacity to modify a translated protein, are relevant requirements for selecting this host cell for protein expression in several pharmaceutical and clinical applications. In particular, Pichia pastoris is used as an industrial host for recombinant protein and metabolite production, showing a powerful capacity to meet required biomolecular target production levels in high-throughput assays for functional genomics and drug screening. In addition, there is a great advantage to using P. pastoris for protein secretion, even at high molecular weights, since the recovery and purification steps are simplified owing to relatively low levels of endogenous proteins in the extracellular medium. Clearly, no single microexpression system can provide all of the desired properties for human protein production. Moreover, chemical and physical bioprocess parameters, including culture medium formulation, temperature, pH, agitation, aeration rates, induction, and feeding strategies, can highly influence product yield and quality. In order to benefit from the currently available wide range of biosynthesis strategies using P. pastoris, this mini review focuses on the developments and technological fermentation achievements, providing both a comparative and an overall integration analysis. The main aim is to highlight the relevance and versatility of the P. pastoris biosystem to the design of more cost-effective microfactories to meet the increasing demands for recombinant membrane proteins and clinical antibodies for several therapeutic applications.

Keywords

References

  1. Abdulaev, N. G., M. P. Popp, M. P., W. C. Smith, and K. D. Ridger. 1997. Functional expression of bovine opsin in the methylotrophic yeast Pichia pastoris. Protein Expr. Purif. 10: 61-69. https://doi.org/10.1006/prep.1996.0704
  2. Andre, N., N. Cherouati, C. Prual, T. Steffan, G. Zeder-Lutz, T. Magnin, et al. 2006. Enhancing functional production of G protein-coupled receptors in Pichia pastoris to levels required for structural studies via a single expression screen. Protein Sci. 15: 1115-1126. https://doi.org/10.1110/ps.062098206
  3. Alisio, A. and M. Mueckler. 2010. Purification and characterization of mammalian glucose transporters expressed in Pichia pastoris. Protein Expr. Purif. 70: 81-87. https://doi.org/10.1016/j.pep.2009.10.011
  4. Asada, H., T. Uemura, T. Yurugi-Kobayashi, M. Shiroishi, T. Shimamura, H. Tsujimoto, et al. 2011. Evaluation of the Pichia pastoris expression system for the production of GPCRs for structural analysis. Microb. Cell Fact. 10: 24. https://doi.org/10.1186/1475-2859-10-24
  5. Barnard, G. C., A. R. Kull, N. S. Sharkey, S. S. Shaikh, A. M. Rittenhour, I. Burnina, et al. 2010. High-throughput screening and selection of yeast cell lines expressing monoclonal antibodies. J. Ind. Microbiol. Biotechnol. 37: 961-971. https://doi.org/10.1007/s10295-010-0746-1
  6. Baumann K., M. Maurer, M. Dragosits, O. Cos, P. Ferrer, and D. Mattanovich. 2008. Hypoxic fed-batch cultivation of Pichia pastoris increases specific and volumetric productivity of recombinant proteins. Biotechnol. Bioeng. 100: 177-183. https://doi.org/10.1002/bit.21763
  7. Bornet, O., F. Alkhalfioui, C. Logez, and R. Wagner. 2012. Overexpression of membrane proteins using Pichia pastoris. Curr. Prot. Protein Sci. DOI: 10.1002/0471140864.ps2902s67.
  8. Brady, C. P., R. L. Shimp, A. P. Miles, M. Whitmore, and A. W. Stowers. 2001. High-level production and purification of P30P2MSP1(19), an important vaccine antigen for malaria, expressed in the methylotrophic yeast Pichia pastoris. Protein Expr. Purif. 23: 468-475. https://doi.org/10.1006/prep.2001.1526
  9. Brierley, R. 1998. Secretion of recombinant human insulin-like growth factor I (IGF-1). Pichia Protocols 103: 149-177. https://doi.org/10.1385/0-89603-421-6:149
  10. Brierley, R. A., C. Bussineau, R. Kosson, A. Melton, and R. S. Sieger. 1990. Fermentation development of recombinant Pichia pastoris expressing the heterologous gene: Bovine lysozyme. Ann. N.Y. Acad. Sci. 589: 350-362. https://doi.org/10.1111/j.1749-6632.1990.tb24257.x
  11. Celik, E. and P. Calik. 2011. Production of recombinant proteins by yeast cells. Biotechnol. Adv. 142: 105-124.
  12. Celik, E., P. Calik, and S. G. Oliver. 2009. Fedbatch methanol feeding strategy for recombinant protein production by Pichia pastoris in the presence of co-substrate sorbitol. Yeast 92: 473-484.
  13. Cereghino, G. P., J. L. Cereghino, C. Ilgen, and J. M. Cregg. 2002. Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr. Opin. Biotech. 13: 329-332. https://doi.org/10.1016/S0958-1669(02)00330-0
  14. Cereghino, G. P., J. L., Cereghino, and A. Sunga. 2001. New selectable marker/auxotrophic host strain combinations for molecular genetic manipulation of Pichia pastoris. Gene 263: 159-169. https://doi.org/10.1016/S0378-1119(00)00576-X
  15. Cereghino, G. P. and J. M. Cregg. 1999. Applications of yeast in biotechnology: Protein production and genetic analysis. Curr. Opin. Biotechnol. 10: 422-427. https://doi.org/10.1016/S0958-1669(99)00004-X
  16. Cereghino, J. L. and J. M. Cregg. 2000. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol. Rev. 24: 45-66. https://doi.org/10.1111/j.1574-6976.2000.tb00532.x
  17. Chung, B. H. and K. S. Park. 1997. Simple approach to reducing proteolysis during secretory production of human parathyroid hormone in Saccharomyces cerevisiae. Biotechnol. Bioeng. 57: 245-249.
  18. Craveiro, R. B., J. D., Ramalho, J. R. Chagas, P. H. M. Wang, D. E. Casarini, J. L. Pesquero, et al. 2006. High expression of human carboxypeptidase M in Pichia pastoris: Purification and partial characterization. Braz. J. Med. Biol. Res. 39: 211-217. https://doi.org/10.1590/S0100-879X2006000200007
  19. Cregg, J. M. and K. R. Madden. 1987. Development of yeast transformation systems and construction of methanol-utilizationdefective mutants of Pichia pastoris by gene disruption. Biol. Res. Ind. Yeast 2: 1-18.
  20. Cregg, J. M., J. L. Cereghino, S. Jianying, and D. Higgins. 2000. Recombinant protein expression in Pichia pastoris. Mol. Biotechnol. 16: 23-52. https://doi.org/10.1385/MB:16:1:23
  21. Cregg, J. M., K. J. Barringer, A. Y. Hessler, and K. R. Madden. 1985. Pichia pastoris as a host system for transformations. Mol. Cell. Biol. 5: 3376-3385.
  22. Daly, R. and M. T. W. Hearn. 2005. Expression of heterologous proteins in Pichia pastoris: A useful experimental tool in protein engineering and production. J. Mol. Recognit. 18: 119-138. https://doi.org/10.1002/jmr.687
  23. D'Anjou, M. C. and A. J. Daugulis. 2000. Mixed-feed exponential feeding for fed-batch culture of recombinant methylotrophic yeast. Biotechnol. Lett. 22: 341-346. https://doi.org/10.1023/A:1005612415737
  24. D'Anjou, M. C. and A. J. Daugulis. 2001. A rational approach to improving productivity in recombinant Pichia pastoris fermentation. Biotechnol. Bioeng. 72: 1-11. https://doi.org/10.1002/1097-0290(20010105)72:1<1::AID-BIT1>3.0.CO;2-T
  25. Damasceno, L. M., I. Pla, H. J. Chang, L. Cohen, G. Ritter, L. J. Old, and C. A. Batt. 2004. An optimized fermentation process for high-level production of single-chain Fv antibody fragment in Pichia pastoris. Protein Expr. Purif. 37: 18-26. https://doi.org/10.1016/j.pep.2004.03.019
  26. Damasceno, L. M., C. J. Huang, and C. Batt. 2012. Protein secretion in Pichia pastoris and advances in protein production. Appl. Microbiol. Biotechnol. 93: 31-39. https://doi.org/10.1007/s00253-011-3654-z
  27. Demain, A. and P. Vaishnav. 2009. Production of recombinant proteins by microbes and higher organisms. Biotechnol. Adv. 27: 297-306. https://doi.org/10.1016/j.biotechadv.2009.01.008
  28. De Rivoyre, D., F. Bonino, L. Ruel, M. Bidet, P. Therond, and I. Mus-Veteau. 1996. Human receptor Smoothened, a mediator of Hedgehog signalling, expressed in its native conformation in yeast. FEBS Lett. 579: 1529-1533.
  29. Dietzsch, C., O. Spadiut, and C. Herwig. 2011. A fast approach to determine a fed batch feeding profile for recombinant Pichia pastoris strains. Microb. Cell Fact. 10: 85. https://doi.org/10.1186/1475-2859-10-85
  30. Dietzsch, C., O. Spadiut, and C. Herwig. 2011. A dynamic method based on the specific substrate uptake rate to set up a feeding strategy for Pichia pastoris. Microb. Cell Fact. 10: 14. https://doi.org/10.1186/1475-2859-10-14
  31. Domingez, A., E. Ferminan, M. Sanchez, F. J. Gonzalez, F. M. Perez-Campo, S. Garcia, et al. 1998. Non-conventional yeast as hosts for heterologous protein production. Int. Microbiol. 1: 131-142.
  32. Dragosits, M., J. Stadlmann, J. Albiol, K. Baumann, M. Maurer, B. Gasser, et al. 2009. The effect of temperature on the proteome of recombinant Pichia pastoris. Analysis 8: 1380-1392.
  33. Eldin, P., M. E. Pauza, Y. Hieda, G. Lin, M. P. Murtaugh, P. R. Pentel, and C. A. Pennell. 1997. High-level secretion of two antibody single chain Fv fragments by Pichia pastoris. J. Immunol. Methods 201: 67-75. https://doi.org/10.1016/S0022-1759(96)00213-X
  34. Faber, K., W. Harder, G. Ab, and M. Veenhuis. 1995. Review: Methylotrophic yeast as factories for the production of foreign proteins. Yeast 11: 1331-1344. https://doi.org/10.1002/yea.320111402
  35. Fan, Y., L. Shi, V. Ladizhansky, and L. S. Brown. 2011. Uniform isotope labeling of a eukaryotic seven-transmembrane helical protein in yeast enables high-resolution solid-state NMR studies in the lipid environment. J. Biomol. NMR 49: 151-161. https://doi.org/10.1007/s10858-011-9473-9
  36. Gellissen, G. 2000. Heterologous protein production in methylotrophic yeasts. Appl. Microbiol. Biotechnol. 54: 741-750. https://doi.org/10.1007/s002530000464
  37. Ghosalkar, A., V. Sahai, and A. Srivastava. 2008. Optimization of chemically defined medium for recombinant Pichia pastoris for biomass production. Bioresour. Technol. 99: 7906-7910. https://doi.org/10.1016/j.biortech.2008.01.059
  38. Gleeson, M. A., C. White, D. P. Meininger, and E. A. Komives. 1998. Generation of protease-deficient strains and their use in heterologous protein expression. Methods Mol. Biol. 103: 81-94.
  39. Goel, A., D. Colcher, J. Baranowska-Kortylewicz, S. Augustine, B. J. M. Booth, G. Pavlinkova, and S. K. Batra. 2000. Genetically engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: Improved biodistribution and potential for therapeutic application. Cancer Res. 60: 6964-6971.
  40. Ha, S., Y. Wang, and R. R. Rustandi. 2011. Biochemical and biophysical characterization of humanized IgG1 produced in Pichia pastoris. MAbs 3: 453-460. https://doi.org/10.4161/mabs.3.5.16891
  41. Hamilton, S. R. and T. U. Tilman. 2007. Glycosylation engineering in yeast: The advent of fully humanized yeast. Curr. Opin. Biotechnol. 18: 387-392. https://doi.org/10.1016/j.copbio.2007.09.001
  42. Hellwing, S., F. Emde, N. Raven, M. Henke, P. Van der Long, and R. Fischer. 2000. Analysis of single-chain antibody production in Pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations. Biotechnol. Bioeng. 74: 344-352.
  43. Hohenblum, H., N. Borth, and D. Mattanovich. 2003. Assessing viability and cell-associated product of recombinant protein producing Pichia pastoris with flow cytometry. J. Biotechnol. 102: 281-290. https://doi.org/10.1016/S0168-1656(03)00049-X
  44. Huang, C. J., L. M. Damasceno, K. A. Anderson, S. Zhang, L. J. Old, and C. A. Batt. 2011. A proteomic analysis of the Pichia pastoris secretome in methanol-induced cultures. Genomics Transcriptomics Proteomics 90: 235-247.
  45. Idiris, A., H. Tohda, H. Kumagai, and K. Takegawa. 2010. Engineering of protein secretion in yeast: Strategies and impact on protein production. Appl. Microbiol. Biotechnol. 86: 403-417. https://doi.org/10.1007/s00253-010-2447-0
  46. Issaly, N., O. Solsona, P. Joudrier, M. F. Gautier, G. Moulin, and H. Boze. 2001. Optimization of the wheat puroindoline-a production in Pichia pastoris. J. Appl. Microbiol. 90: 397-406. https://doi.org/10.1046/j.1365-2672.2001.01259.x
  47. Jafari, R., B. E. Sundstrom, and P. Holm. 2011. Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia pastoris using design of experiments. Microb. Cell Fact. 10: 34. https://doi.org/10.1186/1475-2859-10-34
  48. Jeong, K.J., S. H. Jang, and N. Velmurugan. 2011. Recombinant antibodies: Engineering and production in yeast and bacterial hosts. Biotechnol. J. 6: 16-27. https://doi.org/10.1002/biot.201000381
  49. Jiang, Y., F. Li, D. Zha, T. I. Potgieter, T. Mitchell, R. Moore, et al. 2011. Purification process development of a recombinant monoclonal antibody expressed in glycoengineered Pichia pastoris. Protein Expr. Purif. 76: 7-14. https://doi.org/10.1016/j.pep.2010.11.004
  50. Kato, S., M. Ishibashi, D. Tatsuda, H. Tokunaga, and M. Tokunaga. 2001. Efficient expression, purification and characterization of mouse salivary a-amylase secreted from methylotrophic yeast, Pichia pastoris. Yeast 18: 643-655. https://doi.org/10.1002/yea.714
  51. Kottmeier, K., K. Ostermann, T. Bley, and G. Rodel. 2011. Hydrophobin signal sequence mediates efficient secretion of recombinant proteins in Pichia pastoris. Appl. Microbiol. Biotechnol. 91: 133-141. https://doi.org/10.1007/s00253-011-3246-y
  52. Li, P., A. Anumanthan, X. G. Gao, K. Ilangovan, V. V. Suzara, N. Duzgune , and V. Renugopalakrishnan. 2007. Expression of recombinant proteins in Pichia pastoris. Appl. Biochem. Biotechnol. 142: 105-124. https://doi.org/10.1007/s12010-007-0003-x
  53. Li, T., J. Cheng, B. Hu, Y. Liu, G. Quian, and F. Liu. 2008. Construction, production, and characterization of recombinant scFv antibodies against methamidophos expressed in Pichia pastoris. World J. Microbiol. Biotechnol. 24: 867-874. https://doi.org/10.1007/s11274-007-9554-9
  54. Li, H. and M. d'Anjou. 2009. Pharmacological significance of glycosylation in the therapeutic proteins. Curr. Opin. Biotechnol. 20: 678-684. https://doi.org/10.1016/j.copbio.2009.10.009
  55. Li, Z. J., F. Xiong, Q. Lin, M. d'Anjou, A. J. Daugulis, D. S. Yang, and C. L. Hew. 2001. Low-temperature increases the yield of biologically active herring antifreeze protein in Pichia pastoris. Protein Expr. Purif. 21: 483-445.
  56. Lin, H., T. Kim, F. Xiong, and X. Yang. 2007. Enhancing the production of Fc fusion protein in fed-batch fermentation of Pichia pastoris by design of experiments. Biotechnol. Prog. 23: 621-625.
  57. Macauley-Patrick, S., L. M. Fazenda, B. McNeil, and L. M. Harvey. 2005. Heterologous protein production using the Pichia pastoris expression system. Yeast 22: 249-270. https://doi.org/10.1002/yea.1208
  58. Minning, S., A. Serrano, P. Ferrer, C. Sola, R. D. Schmid, and F. Valero. 2001. Optimization of the high-level production of Rhizopus oryzae lipase in Pichia pastoris. J. Biotechnol. 86: 59-70. https://doi.org/10.1016/S0168-1656(00)00402-8
  59. Müller, K. M., K. M. Arndt, K. Bauer, and A. Plückthun. 1998. Tandem immobilized metal-ion affinity chromatography/ immunoaffinity purification of His-tagged proteins - evaluation of two anti-His-tag monoclonal antibodies. Anal. Biochem. 259: 54-61. https://doi.org/10.1006/abio.1998.2606
  60. Murasugi, A., Y. Asami, and M. Mera-Kikuchi. 2001. Production of recombinant human bile salt-stimulated lipase in Pichia pastoris. Protein Expr. Purif. 23: 282-288. https://doi.org/10.1006/prep.2001.1509
  61. Oehler, R., G. Lesnicki, and M. Galleno. 1998. High cell density fermentation of Pichia pastoris using nonphosphate precipitate forming sodium hexametaphosphate as a phosphate source. Current topics in gene expression annual meeting. SanDiego, CA, USA
  62. Ogunijimi, A., J. Chandler, C. Gooding, A. Recinos, and P. Choudary. 1999. High-level secretory expression of immunologically active intact antibody from yeast Pichia pastoris. Biotechnol. Lett. 21: 561-567. https://doi.org/10.1023/A:1005542011387
  63. Paifer, E., E. Margolles, J. Cremata, R. Montesino, L. Herera, and J. M. Delgado. 1994. Efficient expression and secretion of recombinant alpha amylase in Pichia pastoris using two different signal sequences. Yeast 10: 1415-1419. https://doi.org/10.1002/yea.320101104
  64. Panjideh, H., V. Coelho, J. Dernedde, H. Fuchs, U. Keilholz, E. Thiel, and P. M. Deckert. 2008. Production of bifunctional single-chain antibody-based fusion proteins in Pichia pastoris supernatants. Bioprocess Biosyst. Eng. 31: 559-568. https://doi.org/10.1007/s00449-008-0203-y
  65. Plantz, B. A., K. Nickerson, S. D. Kachman, and V. L. Schlegel. 2007. Evaluation of metals in a defined medium for Pichia pastoris expressing recombinant beta-galactosidase. Biotechnol. Prog. 23: 687-692.
  66. Porro, D., B. Gasser, T. Fossati, M. Maurer, P. Branduardi, M. Sauer, and D. Mattanovich. 2011. Production of recombinant proteins and metabolites in yeasts: When are these systems better than bacterial production systems? Appl. Microbiol. Biotechnol. 89: 939-948. https://doi.org/10.1007/s00253-010-3019-z
  67. Potgieter, T. I., M. Cukan, J. E. Drummond, N. R. Houston-Cummings, Y. Jiang, F. Li, et al. 2009. Production of monoclonal antibodies by glycoengineered Pichia pastoris. J. Biotechnol. 139: 318-325. https://doi.org/10.1016/j.jbiotec.2008.12.015
  68. Powers, D. B., P. Amersdorfer, M. Poul, U. S. Nielsen, M. R. Shalaby, G. P. Adams, et al. 2001. Expression of single-chain Fv-Fc fusions in Pichia pastoris. J. Immunol. Methods 251: 123-135. https://doi.org/10.1016/S0022-1759(00)00290-8
  69. Raman, P., V. Cherezov, and M. Caffrey. 2006. The membrane protein data bank. Cell. Mol. Life Sci. 63: 36-51. https://doi.org/10.1007/s00018-005-5350-6
  70. Ramon, A. and M. Marin. 2011. Advances in the production of membrane proteins in Pichia pastoris. Biotechnol. J. 6: 700-706. https://doi.org/10.1002/biot.201100146
  71. Roque, A. C., C. R. Lowe, and M. A. Taipa. 2004. Antibodies and genetically engineered related molecules: Production and purification. Biotechnol. Progr. 20: 639-654. https://doi.org/10.1021/bp030070k
  72. Routledge, S. J., C. J. Hewitt, N. Bora, and R. M. Bill. 2011. Antifoam addition to shake flask cultures of recombinant Pichia pastoris increases yield. Microb. Cell Fact. 10: 17. https://doi.org/10.1186/1475-2859-10-17
  73. Sarramegna, V., I. Muller, G. Mousseau, C. Froment, B. Monsarrat, A. Milon, and F. Talmont. 2005. Solubilization, purification, and mass spectrometry analysis of the human muopioid receptor expressed in Pichia pastoris. Protein Expr. Purif. 43: 85-93. https://doi.org/10.1016/j.pep.2005.05.007
  74. Shi, X., T. Karbut, M. Chamankhah, M. Alting-Mees, S. M. Hemmingsen, and D. Hegedus. 2003. Optimal conditions for the expression of a single-chain antibody (scFv) gene in Pichia pastoris. Protein Expr. Purif. 28: 321-330. https://doi.org/10.1016/S1046-5928(02)00706-4
  75. Shepard, S., C. Stone, S. Cook, A. Bouvier, G. Boyd, G. Weatherly, et al. 2002. Recovery of intracellular recombinant proteins from the yeast Pichia pastoris by cell permeabilization. J. Biotechnol. 99: 149-160. https://doi.org/10.1016/S0168-1656(02)00182-7
  76. Sinha, J., B. A. Plantz, M. Inan, and M. M. Meagher. 2005. Causes of proteolytic degradation of secreted recombinant proteins produced in methylotrophic yeast Pichia pastoris: Case study with recombinant ovine interferon-tau. Biotechnol. Bioeng. 89: 102-112. https://doi.org/10.1002/bit.20318
  77. Stratton, J., V. Chiruvolu, and M. Meagher. 1998. High celldensity fermentation. Biotechnol. Adv. 103: 107-120.
  78. Tolner, B., L. Smith, R. H. Begent, and K. A. Chester. 2006. Production of recombinant protein in Pichia pastoris by fermentation. Nat. Protoc. 1: 1006-1021. https://doi.org/10.1038/nprot.2006.126
  79. Tschopp, J. F., P. F. Brust, J. M. Cregg, C. A. Stillman, and T. R. Gingeras. 1987. Expression of the LacZ gene from two methanol-regulated promoters in Pichia pastoris. Nucleic Acids Res. 15: 3859-3876. https://doi.org/10.1093/nar/15.9.3859
  80. Tsujikawa, M., K. Okabayashi, M. Morita, and T. Tanabe. 1993. Secretion of a variant of human single-chain urokinase-type plasminogen activator without an N-glycosylation site in the methylotrophic yeast, Pichia pastoris and characterization of the secreted product. Yeast 12: 541-553.
  81. Wegner, G. 1990. Emerging applications of the methylotrophic yeast. FEMS Microbiol. Rev. 7: 279-283.
  82. White, C. E., M. J. Hunter, D. P. Meininger, L. R. White, and E. A. Komives. 1995. Large-scale expression, purification and characterization of small fragments of thrombomodulin - the role of sixth domain and methionine 388. Protein Eng. Des. Sel. 8: 1177-1187. https://doi.org/10.1093/protein/8.11.1177
  83. Wood, M. J. and E. A. Komives. 1999. Production of large quantities of isotopically labeled protein in Pichia pastoris by fermentation. J. Biomol. NMR 13: 149-159. https://doi.org/10.1023/A:1008398313350
  84. Ye, J., J. Ly, K. Watts, A. Hsu, A. Walker, K. McLaughlin, et al. 2011. Optimization of a glycoengineered Pichia pastoris cultivation process for commercial antibody production. Biotechnol. Prog. 27: 1744-1750. https://doi.org/10.1002/btpr.695
  85. Yurugi-Kobayashi, T., H. Asada, M. Shiroishi, T. Shimamura, S. Funamoto, N. Katsuta, et al. 2009. Comparison of functional non-glycosylated GPCRs expression in Pichia pastoris. Biochem. Biophys. Res. Commun. 380: 271-276. https://doi.org/10.1016/j.bbrc.2009.01.053
  86. Zhang, W., M. A. Bevins, B. A. Plantz, L. A. Smith, and M. M. Meagher. 2000. Modelling Pichia pastoris growth on methanol and optimizing the production of a recombinant protein, the heavy-chain fragment C of botulinum neurotoxin, serotype A. Biotechnol. Bioeng. 70: 1-8. https://doi.org/10.1002/1097-0290(20001005)70:1<1::AID-BIT1>3.0.CO;2-Y
  87. Zhang, W., M. Inan, and M. M. Meagher. 2000. Fermentation strategies for recombinant protein expression in the methylotrophic yeast Pichia pastoris. Biotechnol. Bioprocess Eng. 5: 275-287. https://doi.org/10.1007/BF02942184
  88. Zhang, A., J. Luo, T. Zhang, Y. Pan, Y. Tan, C. Fu, and F. Tu. 2009. Recent advances on the GAP promoter derived expression system of Pichia pastoris. Mol. Biol. Rep. 36: 1611-1619. https://doi.org/10.1007/s11033-008-9359-4
  89. Zhang, A. L., T. Y. Zhang, J. X. Luo, S. C. Chen, W. J. Guan, C. Y. Fu, et al. 2007. Constitutive expression of human angiostatin in Pichia pastoris by high-density cell culture. J. Ind. Microbiol. Biotechnol. 34: 117-122. https://doi.org/10.1007/s10295-006-0175-3

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  6. Towards improved membrane protein production in Pichia pastoris: General and specific transcriptional response to membrane protein overexpression vol.31, pp.6, 2013, https://doi.org/10.1016/j.nbt.2014.02.009
  7. Advances and needs for endotoxin-free production strains vol.99, pp.22, 2013, https://doi.org/10.1007/s00253-015-6947-9
  8. Gene Cloning, High-Level Expression, and Characterization of an Alkaline and Thermostable Lipase from Trichosporon coremiiforme V3 vol.25, pp.6, 2013, https://doi.org/10.4014/jmb.1408.08039
  9. With great structure comes great functionality: Understanding and emulating spider silk vol.30, pp.1, 2013, https://doi.org/10.1557/jmr.2014.365
  10. Evaluation of MutS and Mut+ Pichia pastoris Strains for Membrane-Bound Catechol-O-Methyltransferase Biosynthesis vol.175, pp.8, 2013, https://doi.org/10.1007/s12010-015-1551-0
  11. Production of Influenza Virus HA1 Harboring Native-Like Epitopes by Pichia pastoris vol.179, pp.7, 2013, https://doi.org/10.1007/s12010-016-2064-1
  12. Development of simple kinetic models and parameter estimation for simulation of recombinant human serum albumin production by Pichia pastoris vol.15, pp.39, 2013, https://doi.org/10.5897/ajb2015.15121
  13. Biosynthesis and purification of histidine‐tagged human soluble catechol‐O‐methyltransferase vol.91, pp.12, 2013, https://doi.org/10.1002/jctb.4930
  14. Efficient production of recombinant glycoprotein D of herpes simplex virus type 2 in Pichia pastoris and its protective efficacy against viral challenge in mice vol.162, pp.3, 2017, https://doi.org/10.1007/s00705-016-3154-7
  15. Molecular and biochemical characterization of a novel cold-active and metal ion-tolerant GH10 xylanase from frozen soil vol.31, pp.5, 2017, https://doi.org/10.1080/13102818.2017.1359667
  16. Cellular and molecular effects of yeast probiotics on cancer vol.43, pp.1, 2013, https://doi.org/10.1080/1040841x.2016.1179622
  17. A systematic analysis of the expression of the anti-HIV VRC01 antibody in Pichia pastoris through signal peptide optimization vol.149, pp.None, 2013, https://doi.org/10.1016/j.pep.2018.03.013
  18. Quality and cost assessment of a recombinant antibody fragment produced from mammalian, yeast and prokaryotic host cells: A case study prior to pharmaceutical development vol.44, pp.None, 2018, https://doi.org/10.1016/j.nbt.2018.04.006
  19. Efficient production of secretory Streptomyces clavuligerus β-lactamase inhibitory protein (BLIP) in Pichia pastoris vol.8, pp.1, 2013, https://doi.org/10.1186/s13568-018-0586-3
  20. Smoothing membrane protein structure determination by initial upstream stage improvements vol.103, pp.14, 2013, https://doi.org/10.1007/s00253-019-09873-1
  21. Organic Wastes as Feedstocks for Non-Conventional Yeast-Based Bioprocesses vol.7, pp.8, 2013, https://doi.org/10.3390/microorganisms7080229
  22. Comparative genome‐scale analysis of Pichia pastoris variants informs selection of an optimal base strain vol.117, pp.2, 2013, https://doi.org/10.1002/bit.27209
  23. Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation vol.9, pp.4, 2013, https://doi.org/10.3390/vaccines9040328
  24. Optimization of a Recombinant Lectin Production in Pichia pastoris Using Crude Glycerol in a Fed-Batch System vol.9, pp.5, 2013, https://doi.org/10.3390/pr9050876