Cultivation strategies to enhance productivity of Pichia pastoris: A review

Biotechnology Advances

Volumn 33, Issue 6, 2014, Pages 1177-1193

  Looser, V ^a   Bruhlmann, B ^a   Bumbak, F ^a   Stenger, C ^a   Costa, M ^b   Camattari, A ^c   Fotiadis, D ^b   Kovar, K ^a  

^a ZURICH UNIVERSITY OF APPLIED SCIENCES   (Switzerland)

^b UNIVERSITY OF BERN   (Switzerland)

^c AGENCY FOR SCIENCE   (Singapore)

Author keywords

Fermentation; Pichia pastoris; Production process development; Productivity; Recombinant protein

Indexed keywords

FERMENTATION; GENE EXPRESSION; GENES; MOBILE SECURITY; PRODUCT DESIGN; PRODUCTIVITY; PROFESSIONAL ASPECTS; PROTEINS; YEAST;

BIOPROCESS ENGINEERING; HETEROLOGOUS PROTEINS; METHYLOTROPHIC YEASTS; PHYSIOLOGICAL EFFECTS; PICHIA PASTORIS; POST-TRANSLATIONAL PROCESSING; PRODUCTION PROCESS; RECOMBINANT PROTEIN PRODUCTIONS;

RECOMBINANT PROTEINS;

BIOENGINEERING; BIOLOGICAL PRODUCTION; BIOMASS; BIOREACTOR; ENZYME; FERMENTATION; GROWTH RATE; PHYSIOLOGY; PROTEIN; RECOMBINATION; YEAST;

PICHIA PASTORIS;

RECOMBINANT PROTEIN;

BIOMASS; BIOSYNTHESIS; BIOTECHNOLOGY; CELL CULTURE TECHNIQUE; GROWTH, DEVELOPMENT AND AGING; KINETICS; PICHIA; PROCEDURES;

BIOMASS; BIOTECHNOLOGY; CELL CULTURE TECHNIQUES; KINETICS; PICHIA; RECOMBINANT PROTEINS;

EID: 84955189763     PISSN: 07349750     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biotechadv.2015.05.008     Document Type: Review

References (137)

1. Ahmad M., Hirz M., Pichler H., Schwab H. Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production. Appl. Microbiol. Biotechnol. 2014, 98:5301-5317.
2. Aw R., Polizzi K.M. Can too many copies spoil the broth?. Microb. Cell Fact. 2013, 12.
3. Barnard G.C., Kull A.R., Sharkey N.S., Shaikh S.S., Rittenhour A.M., Burnina I., et al. High-throughput screening and selection of yeast cell lines expressing monoclonal antibodies. J. Ind. Microbiol. Biotechnol. 2010, 37:961-971.
4. Barrigon J.M., Valero F., Montesinos J.L. A macrokinetic model-based comparative meta-analysis of recombinant protein production by Pichia pastoris under AOX1 promoter. Biotechnol. Bioeng. 2015, 112:1132-1145.
5. Bhatacharya P., Pandey G., Mukherjee K.J. Production and purification of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) from high cell density cultures of Pichia pastoris. Bioprocess Biosyst. Eng. 2007, 30:305-312.
6. Bornert O., Alkhalfioui F., Logez C., Wagner R. Overexpression of membrane proteins using Pichia pastoris. Curr. Protoc. Protein Sci. 2012, Unit: 29. 10.1002/0471140864.ps2902s67.
7. Brierley RA, Siegel RS, Bussineau CM, Craig WS, Holtz GC, Davis GR, et al. Mixed feed recombinant yeast fermentation. US, Patent WO90034311990.
8. Brühlmann B., Heimen T., Barmettler M., Straumann M., Looser V., Kovar K. On-line estimation of biomass and maintenance during cultivation of recombinant P. pastoris. Development and application of enzymes in biotechnology conference 2015, (April 14-15. Düsseldorf. Germany).
9. Brunel L., Neugnot V., Landucci L., Boze W.N., Moulin G., Bigey F., et al. High-level expression of Candida parapsilosis lipase/acyltransferase in Pichia pastoris. J Biotechnol. 2004, 111:41-50.
10. Buchetics M., Dragosits M., Maurer M., Rebnegger C., Porro D., Sauer M., et al. Reverse engineering of protein secretion by uncoupling of cell cycle phases from growth. Biotechnol. Bioeng. 2011, 108:2403-2412.
11. Byrne B. Pichia pastoris as an expression host for membrane protein structural biology. Curr. Opin. Struct. Biol. 2015, 32C:9-17.
12. Calik P., Ata O., Gunes H., Massahi A., Boy E., Keskin A., et al. Recombinant protein production in Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter: from carbon source metabolism to bioreactor operation parameters. Biochem. Eng. J. 2015, 95:20-36.
13. Camattari A., Weinhandl K., Gudiminchi R.K. Methods for efficient high-throughput screening of protein expression in recombinant Pichia pastoris strains 2014, 113-123. Yeast Metabolic Engineering: Springer.
14. Celik E., Calik P., Oliver S.G. A structured kinetic model for recombinant protein production by Mut(+) strain of Pichia pastoris. Chem. Eng. Sci. 2009, 64:5028-5035.
15. Cereghino J.L., Cregg J.M. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol. Rev. 2000, 24:45-66.
16. Chiruvolu V., Cregg J.M., Meagher M.M. Recombinant protein production in an alcohol oxidase-defective strain of Pichia pastoris in fedbatch fermentations. Enzyme Microb. Technol. 1997, 21:277-283.
17. Cos O., Serrano A., Montesinos J.L., Ferrer P., Cregg J.M., Valero F. Combined effect of the methanol utilization (Mut) phenotype and gene dosage on recombinant protein production in Pichia pastoris fed-batch cultures. J. Biotechnol. 2005, 116:321-335.
18. Cos O., Ramon R., Montesinos J.L., Valero F. Operational strategies, monitoring and control of heterologous protein production in the methylotrophic yeast Pichia pastoris under different promoters: a review. Microb. Cell Fact. 2006, 5:17.
19. Costa M., Rosell A., Álvarez-Marimon E., Zorzano A., Fotiadis D., Palacín M. Expression of human heteromeric amino acid transporters in the yeast Pichia pastoris. Protein Expr. Purif. 2013, 87:35-40.
20. Cregg J.M., Madden K.R. Use of site-specific recombination to regenerate selectable markers. Mol. Gen. Genet. 1989, 219:320-323.
21. Cregg J.M., Madden K.R., Barringer K.J., Thill G.P., Stillman C.A. Functional-characterization of the 2 alcohol oxidase genes from the yeast Pichia pastoris. Mol. Cell. Biol. 1989, 9:1316-1323.
22. Cunha A.E., Clemente J.J., Gomes R., Pinto F., Thomaz M., Miranda S., et al. Methanol induction optimization for scFv antibody fragment production in Pichia pastoris. Biotechnol. Bioeng. 2004, 86:458-467.
23. Curvers S., Brixius P., Klauser T., Thommes J., Weuster-Botz D., Takors R., et al. Human chymotrypsinogen B production with Pichia pastoris by integrated development of fermentation and downstream processing. Part 1. Fermentation. Biotechnol. Prog. 2001, 17:495-502.
24. Curvers S., Linneman J., Klauser T., Wandrey C., Takors R. Recombinant protein production with Pichia pastoris in continuous fermentation - kinetic analysis of growth and product formation. Chem. Ing. Tech. 2001, 73:1615-1621.
25. d'Anjou M.C., Daugulis A.J. A rational approach to improving productivity in recombinant Pichia pastoris fermentation. Biotechnol. Bioeng. 2001, 72:1-11.
26. Delic M., Gongrich R., Mattanovich D., Gasser B. Engineering of protein folding and secretion-strategies to overcome bottlenecks for efficient production of recombinant proteins. Antioxid. Redox Signal. 2014, 21:414-437.
27. Dietzsch C., Spadiut O., Herwig C. A dynamic method based on the specific substrate uptake rate to set up a feeding strategy for Pichia pastoris. Microb. Cell Fact. 2011, 10.
28. Dietzsch C., Spadiut O., Herwig C. A fast approach to determine a fed batch feeding profile for recombinant Pichia pastoris strains. Microb. Cell Fact. 2011, 10.
29. Eon-Duval A., Broly H., Gleixner R. Quality attributes of recombinant therapeutic proteins: an assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnol Prog. 2012, 28:608-622.
30. Fotiadis D., Kanai Y., Palacín M. The SLC3 and SLC7 families of amino acid transporters. Mol. Aspects Med. 2013, 34:139-158.
31. Gasser B., Saloheimo M., Rinas U., Dragosits M., Rodriguez-Carmona E., Baumann K., et al. Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview. Microb. Cell Fact. 2008, 7:11-29.
32. Glick B.R. Metabolic load and heterologous gene-expression. Biotechnol. Adv. 1995, 13:247-261.
33. Graslund S., Nordlund P., Weigelt J., Bray J., Gileadi O., Knapp S., et al. Protein production and purification. Nat. Methods 2008, 5:135-146.
34. Grunberger A., Wiechert W., Kohlheyer D. Single-cell microfluidics: opportunity for bioprocess development. Curr. Opin. Biotechnol. 2014, 29:15-23.
35. Gu L., Zhang J., Liu B., Du G., Chen J. High-level extracellular production of glucose oxidase by recombinant Pichia pastoris using a combined strategy. Appl. Biochem. Biotechnol. 2015, 175:1429-1447.
36. Guan B., Chen F., Lei J., Li Y., Duan Z., Zhu R., et al. Constitutive expression of a rhIL-2-HSA fusion protein in Pichia pastoris using glucose as carbon source. Appl Biochem Biotechnol. 2013, 171:1792-1804.
37. Gudiminchi R.K., Geier M., Glieder A., Camattari A. Screening for cytochrome P450 expression in Pichia pastoris whole cells by P450-carbon monoxide complex determination. Biotechnol. J. 2013, 8:146-152.
38. Gurramkonda C., Polez S., Skoko N., Adnan A., Gabel T., Chugh D., et al. Application of simple fed-batch technique to high-level secretory production of insulin precursor using Pichia pastoris with subsequent purification and conversion to human insulin. Microb. Cell Fact. 2010, 9.
39. Ha S., Wang Y., Rustandi R.R. Biochemical and biophysical characterization of humanized IgG1 produced in Pichia pastoris. MAbs 2011, 3:453-460.
40. Ha S., Wang Y., Rustandi R.R. Biochemical and biophysical characterization of humanized IgG1 produced in Pichia pastoris. MAbs 2011, 453.
41. Hang H.F., Chen W., Guo M.J., Chu J., Zhuang Y.P., Zhang S.L. A simple unstructured model-based control for efficient expression of recombinant porcine insulin precursor by Pichia pastoris. Korean J. Chem. Eng. 2008, 25:1065-1069.
42. Hartner F.S., Glieder A. Regulation of methanol utilisation pathway genes in yeasts. Microb. Cell Fact. 2006, 5:39.
43. Hartner F.S., Ruth C., Langenegger D., Johnson S.N., Hyka P., Lin-Cereghino G.P., et al. Promoter library designed for fine-tuned gene expression in Pichia pastoris. Nucleic Acids Res. 2008, 36:e76.
44. Hedfalk K. Further advances in the production of membrane proteins in Pichia pastoris. Bioengineered 2013, 4:363-367.
45. Hemmerich J., Adelantado N., Barrigon J.M., Ponte X., Hormann A., Ferrer P., et al. Comprehensive clone screening and evaluation of fed-batch strategies in a microbioreactor and lab scale stirred tank bioreactor system: application on Pichia pastoris producing Rhizopus oryzae lipase. Microb. Cell Fact. 2014, 13:36.
46. Herwig C., Marison I., von Stockar U. On-line stoichiometry and identification of metabolic state under dynamic process conditions. Biotechnol. Bioeng. 2001, 75:345-354.
47. Hesketh A.R., Castrillo J.I., Sawyer T., Archer D.B., Oliver S.G. Investigating the physiological response of Pichia (Komagataella) pastoris GS115 to the heterologous expression of misfolded proteins using chemostat cultures. Appl. Microbiol. Biotechnol. 2013, 97:9747-9762.
48. Heyland J., Fu J., Blank L.M., Schmid A. Quantitative physiology of Pichia pastoris during glucose-limited high-cell density fed-batch cultivation for recombinant protein production. Biotechnol. Bioeng. 2010, 107:357-368.
49. Heyland J., Fu J.A., Blank L.M., Schmid A. Carbon metabolism limits recombinant protein production in Pichia pastoris. Biotechnol. Bioeng. 2011, 108:1942-1953.
50. Hohenblum H., Gasser B., Maurer M., Borth N., Mattanovich D. Effects of gene dosage, promoters, and substrates on unfolded protein stress of recombinant Pichia pastoris. Biotechnol. Bioeng. 2004, 85:367-375.
51. Holmes W.J., Darby R.A.J., Wilks M.D.B., Smith R., Bill R.M. Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime. Microb. Cell Fact. 2009, 8.
52. Hyka P., Zullig T., Ruth C., Looser V., Meier C., Klein J., et al. Combined use of fluorescent dyes and flow cytometry to quantify the physiological state of Pichia pastoris during the production of heterologous proteins in high cell density fed-batch cultures. Appl. Environ. Microbiol. 2010, 76:4486-4496.
53. Idiris A., Tohda H., Kumagai H., Takegawa K. Engineering of protein secretion in yeast: strategies and impact on protein production. Appl. Microbiol. Biotechnol. 2010, 86:403-417.
54. Inan M., Meagher M.M. Non-repressing carbon sources for alcohol oxidase (AOX1) promoter of Pichia pastoris. J. Biosci. Bioeng. 2001, 92:585-589.
55. Invitrogen Pichia fermentation process guidelines 2002, 1-11. (Catalog No. K1719-91).
56. Jacobs P.P., Geysens S., Vervecken W., Contreras R., Callewaert N. Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nat. Protoc. 2009, 4:58-70.
57. Jacobs P.P., Inan M., Festjens N., Haustraete J., Van Hecke A., Contreras R., et al. Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under controlled specific growth rate. Microb. Cell Fact. 2010, 9.
58. Jafari R., Sundstrom B.E., Holm P. Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia pastoris using design of experiments. Microb. Cell Fact. 2011, 10.
59. Jahic M., Gustavsson M., Jansen A.K., Martinelle M., Enfors S.O. Analysis and control of proteolysis of a fusion protein in Pichia pastoris fed-batch processes. J. Biotechnol. 2003, 102:45-53.
60. Jahic M., Veide A., Charoenrat T., Teeri T., Enfors S.O. Process technology for production and recovery of heterologous proteins with Pichia pastoris. Biotechnol. Prog. 2006, 22:1465-1473.
61. Jenzsch M., Simutis R., Eisbrenner G., Stückrath I., Lübbert A. Estimation of biomass concentrations in fermentation processes for recombinant protein production. Bioprocess Biosyst. Eng. 2006, 29:19-27.
62. + strain. Enzym. Microb. Technol. 2006, 39:936-944.
63. + strain in transient continuous cultures. J. Biotechnol. 2007, 130:236-246.
64. Khasa Y.P., Khushoo A., Srivastava L., Mukherjee K.J. Kinetic studies of constitutive human granulocyte-macrophage colony stimulating factor (hGM-CSF) expression in continuous culture of Pichia pastoris. Biotechnol. Lett. 2007, 29:1903-1908.
65. Khatri N.K., Hoffmann F. Impact of methanol concentration on secreted protein production in oxygen-limited cultures of recombinant Pichia pastoris. Biotechnol. Bioeng. 2006, 93:871-879.
66. Khatri N.K., Hoffmann F. Oxygen-limited control of methanol uptake for improved production of a single-chain antibody fragment with recombinant Pichia pastoris. Appl. Microbiol. Biotechnol. 2006, 72:492-498.
67. Knepper A., Heiser M., Glauche F., Neubauer P. Robotic platform for parallelized cultivation and monitoring of microbial growth parameters in microwell plates. Jala 2014, 19:593-601.
68. Kobayashi K., Kuwae S., Ohya T., Ohda T., Ohyama M., Tomomitsu K. High level secretion of recombinant human serum albumin by fed-batch fermentation of the methylotrophic yeast, Pichia pastoris, based on optimal methanol feeding strategy. J. Biosci. Bioeng. 2000, 90:280-288.
69. Kovarova K., Zehnder A.J., Egli T. Temperature-dependent growth kinetics of Escherichia coli ML 30 in glucose-limited continuous culture. J. Bacteriol. 1996, 178:4530-4539.
70. Krainer F.W., Dietzsch C., Hajek T., Herwig C., Spadiut O., Glieder A. Recombinant protein expression in Pichia pastoris strains with an engineered methanol utilization pathway. Microb. Cell Fact. 2012, 11:22.
71. Krettler C., Reinhart C., Bevans C.G. Expression of GPCRs in Pichia pastoris for structural studies. Methods Enzymol. 2013, 520:1-29.
72. Lattermann C., Buchs J. Microscale and miniscale fermentation and screening. Curr. Opin. Biotechnol. 2014, 35C:1-6.
73. Li P., Anumanthan A., Gao X.-G., Ilangovan K., Suzara V.V., Düzgüneş N., et al. Expression of recombinant proteins in Pichia pastoris. Appl. Biochem. Biotechnol. 2007, 142:105-124.
74. Liachko I., Dunham M.J. An autonomously replicating sequence for use in a wide range of budding yeasts. FEMS Yeast Res. 2014, 14:364-367.
75. Love J.C., Ronan J.L., Grotenbreg G.M., van der Veen A.G., Ploegh H.L. A microengraving method for rapid selection of single cells producing antigen-specific antibodies. Nat. Biotechnol. 2006, 24:703-707.
76. Love K.R., Panagiotou V., Jiang B., Stadheim T.A., Love J.C. Integrated single-cell analysis shows Pichia pastoris secretes protein stochastically. Biotechnol. Bioeng. 2010, 106:319-325.
77. Love K.R., Politano T.J., Panagiotou V., Jiang B., Stadheim T.A., Love J.C. Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity. PLoS One 2012, 7:e37915.
78. Lundholt B.K., Scudder K.M., Pagliaro L. A simple technique for reducing edge effect in cell-based assays. J. Biomol. Screen. 2003, 8:566-570.
79. Lüthy D., Looser V., Meier C., Hyka P., Kovar K. Novel approaches to the design of processes for enzyme production with recombinant Pichia pastoris. BioTech 2011 and 5th Czech-Swiss Symposium. Prague, Czech Republic 2011, 58. V. Spiwok, O. Schreiberová, L. Paulová, J. Káš (Eds.).
80. Luttmann R., Bracewell D.G., Cornelissen G., Gernaey K.V., Glassey J., Hass V.C., et al. Soft sensors in bioprocessing: a status report and recommendations. Biotechnol. J. 2012, 7:1040-1048.
81. Macauley-Patrick S., Fazenda M.L., McNeil B., Harvey L.M. Heterologous protein production using the Pichia pastoris expression system. Yeast 2005, 22:249-270.
82. Mallem M., Warburton S., Li F., Shandil I., Nylen A., Kim S., et al. Maximizing recombinant human serum albumin production in a Mut(s) Pichia pastoris strain. Biotechnol. Prog. 2014, 30:1488-1496.
83. Marx H., Mecklenbrauker A., Gasser B., Sauer M., Mattanovich D. Directed gene copy number amplification in Pichia pastoris by vector integration into the ribosomal DNA locus. FEMS Yeast Res. 2009, 9:1260-1270.
84. Mattanovich D., Borth N. Applications of cell sorting in biotechnology. Microb. Cell Fact. 2006, 5:12-23.
85. Mattanovich D., Branduardi P., Dato L., Gasser B., Sauer M., Porro D. Recombinant protein production in yeasts. Methods Mol. Biol. 2012, 824:329-358.
86. Mattanovich D., Sauer M., Gasser B. Yeast biotechnology: teaching the old dog new tricks. Microb. Cell Fact. 2014, 13.
87. Maurer M., Kuehleitner M., Gasser B., Mattanovich D. Versatile modeling and optimization of fed batch processes for the production of secreted heterologous proteins with Pichia pastoris. Microb. Cell Fact. 2006, 5:37-47.
88. Mellitzer A., Weis R., Glieder A., Flicker K. Expression of lignocellulolytic enzymes in Pichia pastoris. Microb. Cell Fact. 2012, 11:61.
89. Meury M., Costa M., Harder D., Stauffer M., J.-M.J, Brühlmann B., et al. Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2. PLoS One 2014, 9(10):e109882.
90. Meyer H.-P., Schmidhalter D. Industrial Scale Suspension Culture of Living Cells 2014, John Wiley & Sons.
91. Min C.K., Lee J.W., Chung K.H., Park H.W. Control of specific growth rate to enhance the production of a novel disintegrin, saxatilin, in recombinant Pichia pastoris. J. Biosci. Bioeng. 2010, 110:314-319.
92. Minning S., Serrano A., Ferrer P., Sola C., Schmid R.D., Valero F. Optimization of the high-level production of Rhizopus oryzae lipase in Pichia pastoris. J. Biotechnol. 2001, 86:59-70.
93. Pais J.M., Varas L., Valdes J., Cabello C., Rodriguez L., Mansur M. Modeling of mini-proinsulin production in Pichia pastoris using the AOX promoter. Biotechnol. Lett. 2003, 25:251-255.
94. Panagiotou V., Love K.R., Jiang B., Nett J., Stadheim T., Love J.C. Generation and screening of Pichia pastoris strains with enhanced protein production by use of microengraving. Appl. Environ. Microbiol. 2011, 77:3154-3156.
95. Panula-Perala J., Siurkus J., Vasala A., Wilmanowski R., Casteleijn M.G., Neubauer P. Enzyme controlled glucose auto-delivery for high cell density cultivations in microplates and shake flasks. Microb. Cell Fact. 2008, 7:31.
96. Paulova L., Hyka P., Branska B., Melzoch K., Kovar K. Use of a mixture of glucose and methanol as substrates for the production of recombinant trypsinogen in continuous cultures with Pichia pastoris Mut(+). J. Biotechnol. 2012, 157:180-188.
97. Pla I.A., Damasceno L.M., Vannelli T., Ritter G., Batt C.A., Shuler M.L. Evaluation of Mut(+) and Mut(S) Pichia pastoris phenotypes for high level extracellular scFv expression under feedback control of the methanol concentration. Biotechnol. Prog. 2006, 22:881-888.
98. Posch A.E., Herwig C. Physiological description of multivariate interdependencies between process parameters, morphology and physiology during fed-batch penicillin production. Biotechnol. Prog. 2014, 30:689-699.
99. Potgieter T.I., Cukan M., Drummond J.E., Houston-Cummings N.R., Jiang Y., Li F., et al. Production of monoclonal antibodies by glycoengineered Pichia pastoris. J. Biotechnol. 2009, 139:318-325.
100. Potgieter T.I., Kersey S.D., Mallem M.R., Nylen A.C., d'Anjou M. Antibody expression kinetics in glycoengineered Pichia pastoris. Biotechnol. Bioeng. 2010, 106:918-927.
101. Puxbaum V., Mattanovich D., Gasser B. Quo vadis? The challenges of recombinant protein folding and secretion in Pichia pastoris. Appl. Microbiol. Biotechnol. 2015, 99:2925-2938.
102. Rebnegger C., Graf A.B., Valli M., Steiger M.G., Gasser B., Maurer M., et al. In Pichia pastoris, growth rate regulates protein synthesis and secretion, mating and stress response. Biotechnol. J. 2014, 9:511-525.
103. Ren H., Yuan J.Q., Bellgardt K.H. Macrokinetic model for methylotrophic Pichia pastoris based on stoichiometric balance. J. Biotechnol. 2003, 106:53-68.
104. Resina D., Maurer M., Cos O., Arnau C., Carnicer M., Marx H., et al. Engineering of bottlenecks in Rhizopus oryzae lipase production in Pichia pastoris using the nitrogen source-regulated FLD1 promoter. New Biotechnol. 2009, 25:396-403.
105. Rosell A., Meury M., Álvarez-Marimon E., Costa M., Pérez-Cano L., Zorzano A., et al. Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc. Proc. Natl. Acad. Sci. 2014, 111:2966-2971.
106. + strain. Biotechnol. Bioeng. 2008, 99:368-377.
107. Schmidt-Dannert C., Arnold F.H. Directed evolution of industrial enzymes. Trends Biotechnol. 1999, 17:135-136.
108. Seman W., Bakar S., Bukhari N., Gaspar S., Othman R., Nathan S., et al. High level expression of Glomerella cingulata cutinase in dense cultures of Pichia pastoris grown under fed-batch conditions. J. Biotechnol. 2014, 184:219-228.
109. Singh S., Gras A., Fiez-Vandal C., Martinez M., Wagner R., Byrne B. Large-scale production of membrane proteins in Pichia pastoris: the production of G protein-coupled receptors as a case study. Methods Mol. Biol. 2012, 866:197-207.
110. Singh S., Gras A., Fiez-Vandal C., Martinez M., Wagner R., Byrne B. Screening for high-yielding Pichia pastoris clones: the production of G protein-coupled receptors as a case study. Recombinant protein production in yeast 2012, 65-73. Springer.
111. Sinha J., Plantz B.A., Zhang W.H., Gouthro M., Schlegel V., Liu C.P., et al. Improved production of recombinant ovine interferon-tau by Mut+ strain of Pichia pastoris using an optimized methanol feed profile. Biotechnol Prog. 2003, 19:794-802.
112. Sinha J., Inan M., Fanders S., Taoka S., Gouthro M., Swanson T., et al. Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H(c)): antigen E) by Pichia pastoris. J. Biotechnol. 2007, 127:462-474.
113. Sleiman R.J., Gray P.P., McCall M.N., Codamo J., Sunstrom N.A.S. Accelerated cell line development using two-color fluorescence activated cell sorting to select highly expressing antibody-producing clones. Biotechnol. Bioeng. 2008, 99:578-587.
114. Spadiut O., Herwig C. Dynamics in bioprocess development for Pichia pastoris. Bioengineered 2014, 5:0-1.
115. Spadiut O., Rittmann S., Dietzsch C., Herwig C. Dynamic process conditions in bioprocess development. Eng. Life Sci. 2013, 13:88-101.
116. Spadiut O., Dietzsch C., Herwig C. Determination of a dynamic feeding strategy for recombinant Pichia pastoris strains 2014, 185-194. Yeast Metabolic Engineering: Springer.
117. Spadiut O., Zalai D., Dietzsch C., Herwig C. Quantitative comparison of dynamic physiological feeding profiles for recombinant protein production with Pichia pastoris. Bioprocess Biosyst. Eng. 2014, 37:1163-1172.
118. Story C.M., Papa E., Hu C.-C.A., Ronan J.L., Herlihy K., Ploegh H.L., et al. Profiling antibody responses by multiparametric analysis of primary B cells. Proc. Natl. Acad. Sci. 2008, 105:17902-17907.
119. Stratton J., Chiruvolu V., Meagher M. High cell-density fermentation. Methods Mol. Biol. 1998, 103:107-120.
120. Tolner B., Smith L., Begent R.H., Chester K.A. Production of recombinant protein in Pichia pastoris by fermentation. Nat. Protoc. 2006, 1:1006-1021.
121. Vervecken W., Kaigorodov V., Callewaert N., Geysens S., De Vusser K., Contreras R. In vivo synthesis of mammalian-like, hybrid-type N-glycans in Pichia pastoris. Appl. Environ. Microbiol. 2004, 70:2639-2646.
122. Vogl T., Glieder A. Regulation of Pichia pastoris promoters and its consequences for protein production. New Biotechnol. 2013, 30:385-404.
123. Vogl T., Hartner F.S., Glieder A. New opportunities by synthetic biology for biopharmaceutical production in Pichia pastoris. Curr. Opin. Biotechnol. 2013, 24:1094-1101.
124. Wang X., Sun Y., Ke F., Zhao H., Liu T., Xu L., et al. Constitutive expression of Yarrowia lipolytica lipase LIP2 in Pichia pastoris using GAP as promoter. Appl Biochem Biotechnol. 2012, 166:1355-1367.
125. Weinhandl K., Winkler M., Glieder A., Camattari A. A novel multi-enzymatic high throughput assay for transaminase activity. Tetrahedron 2012, 68:7586-7590.
126. Weis R., Luiten R., Skranc W., Schwab H., Wubbolts M., Glieder A. Reliable high-throughput screening with Pichia pastoris by limiting yeast cell death phenomena. FEMS Yeast Res. 2004, 5:179-189.
127. Wilming A., Bahr C., Kamerke C., Buchs J. Fed-batch operation in special microtiter plates: a new method for screening under production conditions. J. Ind. Microbiol. Biotechnol. 2014, 41:513-525.
128. Wu D., Chu J., Hao Y.Y., Wang Y.H., Zhuang Y.P., Zhang S.L. High efficient production of recombinant human consensus interferon mutant in high cell density culture of Pichia pastoris using two phases methanol control. Process Biochem. 2011, 46:1663-1669.
129. Wu D., Chu J., Hao Y.Y., Wang Y.H., Zhuang Y.P., Zhang S.L. Incomplete protein disulphide bond conformation and decreased protein expression result from high cell growth during heterologous protein expression in Pichia pastoris. J. Biotechnol. 2012, 157:107-112.
130. Yamawaki S., Matsumoto T., Ohnishi Y., Kumada Y., Shiomi N., Katsuda T., et al. Production of single-chain variable fragment antibody (scFv) in fed-batch and continuous culture of Pichia pastoris by two different methanol feeding methods. J. Biosci. Bioeng. 2007, 104:403-407.
131. Zalai D., Dietzsch C., Herwig C., Spadiut O. A dynamic fed batch strategy for a Pichia pastoris mixed feed system to increase process understanding. Biotechnol. Prog. 2012, 28:878-886.
132. Zhang W., Bevins M.A., Plantz B.A., Smith L.A., Meagher M.M. Modeling 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. 2000, 70:1-8.
133. Zhang W., Sinha J., Smith L.A., Inan M., Meagher M.M. Maximization of production of secreted recombinant proteins in Pichia pastoris fed-batch fermentation. Biotechnol. Prog. 2005, 21:386-393.
134. Zhang W., Inan M., Meagher M.M. Rational design and optimization of fed-batch and continuous fermentations. Methods Mol. Biol. 2007, 389:43-64.
135. Zhang A.L., Luo J.X., Zhang T.Y., Pan Y.W., Tan Y.H., Fu C.Y., et al. Recent advances on the GAP promoter derived expression system of Pichia pastoris. Mol. Biol. Rep. 2009, 36:1611-1619.
136. Zhou X.S., Zhang Y.X. Decrease of proteolytic degradation of recombinant hirudin produced by Pichia pastoris by controlling the specific growth rate. Biotechnol. Lett. 2002, 24:1449-1453.
137. Zhu T., Guo M., Tang Z., Zhang M., Zhuang Y., Chu J., et al. Efficient generation of multi-copy strains for optimizing secretory expression of porcine insulin precursor in yeast Pichia pastoris. J. Appl. Microbiol. 2009, 107:954-963.