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Molecular Biotechnology

, Volume 61, Issue 5, pp 365–384 | Cite as

Yeast Expression Systems: Overview and Recent Advances

  • Roghayyeh Baghban
  • Safar FarajniaEmail author
  • Masoumeh RajabibazlEmail author
  • Younes Ghasemi
  • AmirAli Mafi
  • Reyhaneh Hoseinpoor
  • Leila Rahbarnia
  • Maryam Aria
Review
  • 442 Downloads

Abstract

Yeasts are outstanding hosts for the production of functional recombinant proteins with industrial or medical applications. Great attention has been emerged on yeast due to the inherent advantages and new developments in this host cell. For the production of each specific product, the most appropriate expression system should be identified and optimized both on the genetic and fermentation levels, considering the features of the host, vector and expression strategies. Currently, several new systems are commercially available; some of them are private and need licensing. The potential for secretory expression of heterologous proteins in yeast proposed this system as a candidate for the production of complex eukaryotic proteins. The common yeast expression hosts used for recombinant proteins’ expression include Saccharomyces cerevisiae, Pichia pastoris, Hansenula polymorpha, Yarrowia lipolytica, Arxula adeninivorans, Kluyveromyces lactis, and Schizosaccharomyces pombe. This review is dedicated to discuss on significant characteristics of the most common methylotrophic and non-methylotrophic yeast expression systems with an emphasis on their advantages and new developments.

Keywords

Expression system Saccharomyces cerevisiae Yarrowia lipolytica Pichia pastoris Hansenula polymorpha 

Notes

Acknowledgements

This study was supported by a Grant from the Biotechnology Research Center Tabriz University of Medical Science.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kim, H. J., & Kim, H. J. (2016). Yeast as an expression system for producing virus-like particles: What factors do we need to consider? Letters in Applied Microbiology, 64, 111–123.Google Scholar
  2. 2.
    Han, M., & Yu, X. (2015). Enhanced expression of heterologous proteins in yeast cells via the modification of N-glycosylation sites. Bioengineered, 6, 115–118.Google Scholar
  3. 3.
    Nielsen, J. (2013). Production of biopharmaceutical proteins by yeast: Advances through metabolic engineering. Bioengineered, 4, 207–211.Google Scholar
  4. 4.
    Baghban, R., Farajnia, S., Ghasemi, Y., Mortazavi, M., Zarghami, N., & Samadi, N. (2018). New developments in Pichia pastoris expression system, review and update. Current Pharmaceutical Biotechnology, 19, 451–467.Google Scholar
  5. 5.
    Llopis, S., Hernandez-Haro, C., Monteoliva, L., Querol, A., Molina, M., & Fernández-Espinar, M. T. (2014). Pathogenic potential of Saccharomyces strains isolated from dietary supplements. PLoS ONE, 9, 1–21.Google Scholar
  6. 6.
    Çelik, E., & Çalık, P. (2012). Production of recombinant proteins by yeast cells. Biotechnology Advances, 30, 1108–1118.Google Scholar
  7. 7.
    Matheson, K., Parsons, L., & Gammie, A. (2017). Whole-genome sequence and variant analysis of W303, a widely-used strain of Saccharomyces cerevisiae. G3 Genes Genomes Genetics, 7, 2219–2226.Google Scholar
  8. 8.
    Duina, A. A., Miller, M. E., & Keeney, J. B. (2014). Budding yeast for budding geneticists: A primer on the Saccharomyces cerevisiae model system. Genetics, 197, 33–48.Google Scholar
  9. 9.
    Tesfaw, A., & Assefa, F. (2014) Current trends in bioethanol production by Saccharomyces cerevisiae: Substrate, inhibitor reduction, growth variables, coculture, and immobilization. International Scholarly Research Notices.  https://doi.org/10.1155/2014/532852.Google Scholar
  10. 10.
    Liu, Z., Tyo, K. E., Martínez, J. L., Petranovic, D., & Nielsen, J. (2012). Different expression systems for production of recombinant proteins in Saccharomyces cerevisiae. Biotechnology and Bioengineering, 109, 1259–1268.Google Scholar
  11. 11.
    Hahn-Hägerdal, B., Karhumaa, K., Fonseca, C., Spencer-Martins, I., & Gorwa-Grauslund, M. F. (2007). Towards industrial pentose-fermenting yeast strains. Applied Microbiology and Biotechnology, 74, 937–953.Google Scholar
  12. 12.
    Biddick, R., & Young, E. T. (2009). The disorderly study of ordered recruitment. Yeast, 26, 205–220.Google Scholar
  13. 13.
    Hohmann, S., Krantz, M., & Nordlander, B. (2007) Yeast osmoregulation. Methods in Enzymology, 428, 29–45.Google Scholar
  14. 14.
    Murakami, C., & Kaeberlein, M. (2009). Quantifying yeast chronological life span by outgrowth of aged cells. Journal of Visualized Experiments, 27, 1–4.Google Scholar
  15. 15.
    Owsianowski, E., Walter, D., & Fahrenkrog, B. (2008). Negative regulation of apoptosis in yeast. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1783, 1303–1310.Google Scholar
  16. 16.
    Brocard-Masson, C., & Dumas, B. (2006). The fascinating world of steroids: S. cerevisiae as a model organism for the study of hydrocortisone biosynthesis. Biotechnology and Genetic Engineering Reviews, 22, 213–252.Google Scholar
  17. 17.
    López-Mirabal, H. R., & Winther, J. R. (2008). Redox characteristics of the eukaryotic cytosol. Biochimica et Biophysica Acta Molecular Cell Research, 1783, 629–640.Google Scholar
  18. 18.
    Nasheuer, H.-P., Smith, R., Bauerschmidt, C., Grosse, F., & Weisshart, K. (2002). Initiation of eukaryotic DNA replication: Regulation and mechanisms. Progress in Nucleic Acid Research and Molecular Biology, 72, 41–94.Google Scholar
  19. 19.
    Munoz, A. J., Wanichthanarak, K., Meza, E., & Petranovic, D. (2012). Systems biology of yeast cell death. FEMS Yeast Research, 12, 249–265.Google Scholar
  20. 20.
    Miller-Fleming, L., Giorgini, F., & Outeiro, T. F. (2008). Yeast as a model for studying human neurodegenerative disorders. Biotechnology Journal, 3, 325–338.Google Scholar
  21. 21.
    Reggiori, F., & Klionsky, D. J. (2013). Autophagic processes in yeast: Mechanism, machinery and regulation. Genetics, 194, 341–361.Google Scholar
  22. 22.
    Karathia, H., Vilaprinyo, E., Sorribas, A., & Alves, R. (2011). Saccharomyces cerevisiae as a model organism: A comparative study. PLoS ONE, 6, 1–10.Google Scholar
  23. 23.
    Tang, H., Wang, S., Wang, J., Song, M., Xu, M., Zhang, M., Shen, Y., Hou, J., & Bao, X. (2016). N-hypermannose glycosylation disruption enhances recombinant protein production by regulating secretory pathway and cell wall integrity in Saccharomyces cerevisiae. Scientific Reports 6, 1–13.Google Scholar
  24. 24.
    Ahmad, M., Hirz, M., Pichler, H., & Schwab, H. (2014). Protein expression in Pichia pastoris: Recent achievements and perspectives for heterologous protein production. Applied Microbiology and Biotechnology, 98, 5301–5317.Google Scholar
  25. 25.
    Demain, A. L., & Vaishnav, P. (2009). Production of recombinant proteins by microbes and higher organisms. Biotechnology Advances, 27, 297–306.Google Scholar
  26. 26.
    Xie,Y.,Han,X.andMiao,Y.(2018)An effective recombinant protein expression and purification system in Saccharomyces cerevisiae. Current Protocols in Molecular Biology, 123, 1–16.Google Scholar
  27. 27.
    Muñoz, P., Bouza, E., Cuenca-Estrella, M., Eiros, J. M., Pérez, M. J., Sánchez-Somolinos, M., Rincón, C., Hortal, J., & Peláez, T. (2005). Saccharomyces cerevisiae fungemia: An emerging infectious disease. Clinical Infectious Diseases, 40, 1625–1634.Google Scholar
  28. 28.
    Bekatorou, A., Psarianos, C., & Koutinas, A. A. (2006). Production of food grade yeasts. Food Technology and Biotechnology, 44, 407–415.Google Scholar
  29. 29.
    Mortimer, R. K., & Johnston, J. R. (1986). Genealogy of principal strains of the yeast genetic stock center. Genetics, 113, 35–43.Google Scholar
  30. 30.
    Schacherer, J., Ruderfer, D. M., Gresham, D., Dolinski, K., Botstein, D., & Kruglyak, L. (2007). Genome-wide analysis of nucleotide-level variation in commonly used Saccharomyces cerevisiae strains. PLoS ONE, 2, 1–7.Google Scholar
  31. 31.
    Charron, M. J., Dubin, R. A., & Michels, C. A. (1986). Structural and functional analysis of the MAL1 locus of Saccharomyces cerevisiae. Molecular and Cellular Biology, 6, 3891–3899.Google Scholar
  32. 32.
    Gagiano, M., Bauer, F. F., & Pretorius, I. S. (2002). The sensing of nutritional status and the relationship to filamentous growth in Saccharomyces cerevisiae. FEMS Yeast Research, 2, 433–470.Google Scholar
  33. 33.
    Hanscho, M., Ruckerbauer, E., Chauhan, D., Hofbauer, N. F., Krahulec, H., Nidetzky, S., Kohlwein, B. D., Zanghellini, S., Natter, J., K (2012). Nutritional requirements of the BY series of Saccharomyces cerevisiae strains for optimum growth. FEMS Yeast Research, 12, 796–808.Google Scholar
  34. 34.
    Van Dijken, J., Bauer, J., Brambilla, L., Duboc, P., Francois, J., Gancedo, C., Giuseppin, M., Heijnen, J., Hoare, M., & Lange, H. (2000). An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains. Enzyme and Microbial Technology, 26, 706–714.Google Scholar
  35. 35.
    Nomura, M., Nakamori, S., & Takagi, H. (2003). Characterization of novel acetyltransferases found in budding and fission yeasts that detoxify a proline analogue, azetidine-2-carboxylic acid. Journal of Biochemistry, 133, 67–74.Google Scholar
  36. 36.
    Williams, R. M., Primig, M., Washburn, B. K., Winzeler, E. A., Bellis, M., de Menthiere, C. S., Davis, R. W., & Esposito, R. E. (2002). The Ume6 regulon coordinates metabolic and meiotic gene expression in yeast. Proceedings of the National Academy of Sciences of the United States of America, 99, 13431–13436.Google Scholar
  37. 37.
    Young, C. L., Raden, D. L., & Robinson, A. S. (2013). Analysis of ER resident proteins in Saccharomyces cerevisiae: Implementation of H/KDEL retrieval sequences. Traffic, 14, 365–381.Google Scholar
  38. 38.
    Madzak, C., & Beckerich, J.-M. (2013) Heterologous protein expression and secretion. In G. Barth (Eds.), Yarrowia lipolytica. Microbiology monographs (Vol. 25, pp. 1–76). Berlin: Springer.Google Scholar
  39. 39.
    Santos, E. O., Michelon, M., Gallas, J. A., Kalil, S. J., & Burkert, C. A. V. (2013). Raw glycerol as substrate for the production of yeast biomass. International Journal of Food Engineering, 9, 413–420.Google Scholar
  40. 40.
    Bonnet, C., Rigaud, C., Chanteclaire, E., Blandais, C., Tassy-Freches, E., Arico, C., & Javaud, C. (2013). PCR on yeast colonies: An improved method for glyco-engineered Saccharomyces cerevisiae. BMC Research Notes, 6, 1–9.Google Scholar
  41. 41.
    Piirainen, M. A., Boer, H., de Ruijter, J. C., & Frey, A. D. (2016). A dual approach for improving homogeneity of a human-type N-glycan structure in Saccharomyces cerevisiae. Glycoconjugate Journal, 33, 189–199.Google Scholar
  42. 42.
    DiCarlo, J. E., Norville, J. E., Mali, P., Rios, X., Aach, J., & Church, G. M. (2013). Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic Acids Research, 41, 4336–4343.Google Scholar
  43. 43.
    Madzak, C., Gaillardin, C., & Beckerich, J.-M. (2004). Heterologous protein expression and secretion in the non-conventional yeast Yarrowia lipolytica: A review. Journal of Biotechnology, 109, 63–81.Google Scholar
  44. 44.
    Groenewald, M., Boekhout, T., Neuvéglise, C., Gaillardin, C., Van Dijck, P. W., & Wyss, M. (2014). Yarrowia lipolytica: Safety assessment of an oleaginous yeast with a great industrial potential. Critical Reviews in Microbiology, 40, 187–206.Google Scholar
  45. 45.
    Trassaert, M., Vandermies, M., Carly, F., Denies, O., Thomas, S., Fickers, P., & Nicaud, J.-M. (2017). New inducible promoter for gene expression and synthetic biology in Yarrowia lipolytica. Microbial Cell Factories, 16, 1–17.Google Scholar
  46. 46.
    Madzak, C. (2015). Yarrowia lipolytica: Recent achievements in heterologous protein expression and pathway engineering. Applied Microbiology and Biotechnology, 99, 4559–4577.Google Scholar
  47. 47.
    Ryu, S., Hipp, J., & Trinh, C. T. (2016). Activating and elucidating metabolism of complex sugars in Yarrowia lipolytica. Applied and Environmental Microbiology, 82, 1334–1345.Google Scholar
  48. 48.
    Zimmermann, R., Eyrisch, S., Ahmad, M., & Helms, V. (2011). Protein translocation across the ER membrane. Biochimica et Biophysica Acta, 1808, 912–924.Google Scholar
  49. 49.
    Cui, W., Wang, Q., Zhang, F., Zhang, S. C., Chi, Z. M., & Madzak, C. (2011). Direct conversion of inulin into single cell protein by the engineered Yarrowia lipolytica carrying inulinase gene. Process Biochemistry, 46, 1442–1448.Google Scholar
  50. 50.
    Liu, X. Y., Chi, Z., Liu, G. L., Wang, F., Madzak, C., & Chi, Z. M. (2010). Inulin hydrolysis and citric acid production from inulin using the surfaceengineered Yarrowia lipolytica displaying inulinase. Metabolic Engineering, 12, 469–476.Google Scholar
  51. 51.
    Looser, V., Bruhlmann, B., Bumbak, F., Stenger, C., Costa, M., Camattari, A., Fotiadis, D., & Kovar, K. (2015). Cultivation strategies to enhance the productivity of Pichia pastoris: A review. Biotechnology Advances, 33, 1177–1193.Google Scholar
  52. 52.
    Irani, Z. A., Kerkhoven, E. J., Shojaosadati, S. A., & Nielsen, J. (2016). Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins. Biotechnology and Bioengineering, 113, 961–969.Google Scholar
  53. 53.
    Schmidt, F. (2004). Recombinant expression systems in the pharmaceutical industry. Applied Microbiology and Biotechnology, 65, 363–372.Google Scholar
  54. 54.
    Vieira, S. M., da Rocha, S. L. G., da Neves-Ferreira, A. G., Almeida, R. V., & Perales, J. (2017). Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris. PLoS Neglected Tropical Diseases, 11, 1–20.Google Scholar
  55. 55.
    Potvin, G., Ahmad, A., & Zhang, Z. (2012). Bioprocess engineering aspects of heterologous protein production in Pichia pastoris: A review. Biochemical Engineering Journal, 64, 91–105.Google Scholar
  56. 56.
    Baghban, R., Gargari, S. L. M., Rajabibazl, M., Nazarian, S., & Bakherad, H. (2016). Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris. Applied Biochemistry and Biotechnology, 63, 200–205.Google Scholar
  57. 57.
    Xia, W.-R., Fu, W.-L., Cai, L., Cai, X., Wang, Y.-Y., Zou, M.-J., & Xu, D.-G. (2012). Expression, purification and characterization of recombinant human angiogenin in Pichia pastoris. Bioscience, Biotechnology, and Biochemistry, 76, 1384–1388.Google Scholar
  58. 58.
    Rothan, H. A., Teh, S. H., Haron, K., & Mohamed, Z. (2012). A comparative study on the expression, purification and functional characterization of human adiponectin in Pichia pastoris and Escherichia coli. International Journal of Molecular Sciences, 13, 3549–3562.Google Scholar
  59. 59.
    Fan, G., Katrolia, P., Jia, H., Yang, S., Yan, Q., & Jiang, Z. (2012). High-level expression of a xylanase gene from the thermophilic fungus Paecilomyces thermophila in Pichia pastoris. Biotechnology Letters, 34, 2043–2048.Google Scholar
  60. 60.
    Gach, J. S., Maurer, M., Hahn, R., Gasser, B., Mattanovich, D., Katinger, H., & Kunert, R. (2007). High level expression of a promising anti-idiotypic antibody fragment vaccine against HIV-1 in Pichia pastoris. Journal of Biotechnology, 128, 735–746.Google Scholar
  61. 61.
    Cregg, J. M., Cereghino, J. L., Shi, J., & Higgins, D. R. (2000). Recombinant protein expression in Pichia pastoris. Molecular Biotechnology, 16, 23–52.Google Scholar
  62. 62.
    Fickers, P. (2014). Pichia pastoris: A workhorse for recombinant protein production. Current Research in Microbiology and Biotechnology, 2, 354–363.Google Scholar
  63. 63.
    Cos, O., Serrano, A., Montesinos, J. L., Ferrer, P., Cregg, J. M., & Valero, F. (2005). Combined effect of the methanol utilization (Mut) phenotype and gene dosage on recombinant protein production in Pichia pastoris fed-batch cultures. Journal of Biotechnology, 116, 321–335.Google Scholar
  64. 64.
    Daly, R., & Hearn, M. T. (2005). Expression of heterologous proteins in Pichia pastoris: A useful experimental tool in protein engineering and production. Journal of Molecular Recognition: An Interdisciplinary Journal, 18, 119–138.Google Scholar
  65. 65.
    Yin, J., Li, G., Ren, X., & Herrler, G. (2007). Select what you need: A comparative evaluation of the advantages and limitations of frequently used expression systems for foreign genes. Journal of Biotechnology, 127, 335–347.Google Scholar
  66. 66.
    Vanz, A., Lünsdorf, H., Adnan, A., Nimtz, M., Gurramkonda, C., Khanna, N., & Rinas, U. (2012). Physiological response of Pichia pastoris GS115 to methanol-induced high level production of the Hepatitis B surface antigen: Catabolic adaptation, stress responses, and autophagic processes. Microbial Cell Factories, 11, 1–11.Google Scholar
  67. 67.
    Charoenrat, T., Khumruaengsri, N., Promdonkoy, P., Rattanaphan, N., Eurwilaichitr, L., Tanapongpipat, S., & Roongsawang, N. (2013). Improvement of recombinant endoglucanase produced in Pichia pastoris KM71 through the use of synthetic medium for inoculum and pH control of proteolysis. Journal of Bioscience and Bioengineering, 116, 193–198.Google Scholar
  68. 68.
    Stöckmann, C., Scheidle, M., Dittrich, B., Merckelbach, A., Hehmann, G., Melmer, G., Klee, D., Büchs, J., Kang, H. A., & Gellissen, G. (2009). Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment. Microbial Cell Factories, 8, 1–10.Google Scholar
  69. 69.
    Weninger, A., Hatzl, A.-M., Schmid, C., Vogl, T., & Glieder, A. (2016). Combinatorial optimization of CRISPR/Cas9 expression enables precision genome engineering in the methylotrophic yeast Pichia pastoris. Journal of Biotechnology, 235, 139–149.Google Scholar
  70. 70.
    Zahrl, R. J., Peña, D. A., Mattanovich, D., & Gasser, B. (2017). Systems biotechnology for protein production in Pichia pastoris. FEMS Yeast Research, 17, 1–31.Google Scholar
  71. 71.
    Vogl, T., Ahmad, M., Krainer, F. W., Schwab, H., & Glieder, A. (2015). Restriction site free cloning (RSFC) plasmid family for seamless, sequence independent cloning in Pichia pastoris. Microbial Cell Factories, 14, 1–15.Google Scholar
  72. 72.
    Prielhofer, R., Barrero, J. J., Steuer, S., Gassler, T., Zahrl, R., Baumann, K., Sauer, M., Mattanovich, D., Gasser, B., & Marx, H. (2017). Golden Pi CS: A Golden Gate-derived modular cloning system for applied synthetic biology in the yeast Pichia pastoris. BMC Systems Biology, 11, 1–14.Google Scholar
  73. 73.
    Suwannarangsee, S., Kim, S., Kim, O.-C., Oh, D.-B., Seo, J.-W., Kim, C. H., Rhee, S. K., Kang, H. A., Chulalaksananukul, W., & Kwon, O. (2012). Characterization of alcohol dehydrogenase 3 of the thermotolerant methylotrophic yeast Hansenula polymorpha. Applied Microbiology and Biotechnology, 96, 697–709.Google Scholar
  74. 74.
    Ishchuk, O. P., Voronovsky, A. Y., Stasyk, O. V., Gayda, G. Z., Gonchar, M. V., Abbas, C. A., & Sibirny, A. A. (2008). Overexpression of pyruvate decarboxylase in the yeast Hansenula polymorpha results in increased ethanol yield in high-temperature fermentation of xylose. FEMS Yeast Research, 8, 1164–1174.Google Scholar
  75. 75.
    Sohn, M. J., Oh, D. B., Kim, E. J., Cheon, S. A., Kwon, O., Kim, J. Y., Lee, S. Y., & Kang, H. A. (2012). HpYPS1 and HpYPS7 encode functional aspartyl proteases localized at the cell surface in the thermotolerant methylotrophic yeast Hansenula polymorpha. Yeas., 29, 1–16.Google Scholar
  76. 76.
    Park, J.-N., Sohn, M. J., Oh, D.-B., Kwon, O., Rhee, S. K., Hur, C.-G., Lee, S. Y., Gellissen, G., & Kang, H. A. (2007). Identification of the cadmium-inducible Hansenula polymorpha SEO1 gene promoter by transcriptome analysis and its application to whole-cell heavy-metal detection systems. Applied and Environmental Microbiology, 73, 5990–6000.Google Scholar
  77. 77.
    Kim, M. W., Kim, E. J., Kim, J.-Y., Park, J.-S., Oh, D.-B., Shimma, Y., Chiba, Y., Jigami, Y., Rhee, S. K., & Kang, H. A. (2006). Functional characterization of the Hansenula polymorpha HOC1, OCH1, and OCR1 genes as members of the yeast OCH1 mannosyltransferase family involved in protein glycosylation. Journal of Biological Chemistry, 281, 6261–6272.Google Scholar
  78. 78.
    Oh, D. B., Park, J. S., Kim, M. W., Cheon, S. A., Kim, E. J., Moon, H. Y., Kwon, O., Rhee, S. K., & Kang, H. A. (2008). Glycoengineering of the methylotrophic yeast Hansenula polymorpha for the production of glycoproteins with trimannosyl core N-glycan by blocking core oligosaccharide assembly. Biotechnology Journal: Healthcare Nutrition Technology., 3, 659–668.Google Scholar
  79. 79.
    Gellissen, G., Kunze, G., Gaillardin, C., Cregg, J. M., Berardi, E., Veenhuis, M., & van der Klei, I. (2005). New yeast expression platforms based on methylotrophic Hansenula polymorpha and Pichia pastoris and on dimorphic Arxula adeninivorans and Yarrowia lipolytica–a comparison. FEMS Yeast Research, 5, 1079–1096.Google Scholar
  80. 80.
    Mayer, A., Hellmuth, K., Schlieker, H., Lopez-Ulibarri, R., Oertel, S., Dahlems, U., Strasser, A., & Van Loon, A. (1999). An expression system matures: A highly efficient and cost-effective process for phytase production by recombinant strains of Hansenula polymorpha. Biotechnology and Bioengineering, 63, 373–381.Google Scholar
  81. 81.
    Stoyanov, A., Petrova, P., Lyutskanova, D., & Lahtchev, K. (2014). Structural and functional analysis of PUR2, 5 gene encoding bifunctional enzyme of de novo purine biosynthesis in Ogataea (Hansenula) polymorpha CBS 4732 T. Microbiological Research, 169, 378–387.Google Scholar
  82. 82.
    Ravin, N. V., Eldarov, M. A., Kadnikov, V. V., Beletsky, A. V., Schneider, J., Mardanova, E. S., Smekalova, E. M., Zvereva, M. I., Dontsova, O. A., & Mardanov, A. V. (2013). Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1. BMC Genomics, 14, 1–20.Google Scholar
  83. 83.
    Ishchuk, O. P., Voronovsky, A. Y., Abbas, C. A., & Sibirny, A. A. (2009). Construction of Hansenula polymorpha strains with improved thermotolerance. Biotechnology and Bioengineering, 104, 911–919.Google Scholar
  84. 84.
    Péter, G., Tornai-Lehoczki, J., Shin, K. S., & Dlauchy, D. (2007). Ogataea thermophila sp. nov., the teleomorph of Candida thermophila. FEMS Yeast Research, 7, 494–496.Google Scholar
  85. 85.
    Kata, I., Semkiv, M. V., Ruchala, J., Dmytruk, K. V., & Sibirny, A. A. (2016). Overexpression of the genes PDC1 and ADH1 activates glycerol conversion to ethanol in the thermotolerant yeast Ogataea (Hansenula) polymorpha. Yeast, 33, 471–478.Google Scholar
  86. 86.
    Ryabova, O. B., Chmil, O. M., & Sibirny, A. A. (2003). Xylose and cellobiose fermentation to ethanol by the thermotolerant methylotrophic yeast Hansenula polymorpha. FEMS Yeast Research, 4, 157–164.Google Scholar
  87. 87.
    Voronovsky, A. Y., Ryabova, O. B., Verba, O. V., Ishchuk, O. P., Dmytruk, K. V., & Sibirny, A. A. (2005). Expression of xylA genes encoding xylose isomerases from Escherichia coli and Streptomyces coelicolor in the methylotrophic yeast Hansenula polymorpha. FEMS Yeast Research, 5, 1055–1062.Google Scholar
  88. 88.
    Ruchala, J., Kurylenko, O. O., Soontorngun, N., Dmytruk, K. V., & Sibirny, A. A. (2017). Transcriptional activator Cat8 is involved in regulation of xylose alcoholic fermentation in the thermotolerant yeast Ogataea (Hansenula) polymorpha. Microbial Cell Factories, 16, 1–13.Google Scholar
  89. 89.
    Steinborn, G., Böer, E., Scholz, A., Tag, K., Kunze, G., & Gellissen, G. (2006). Application of a wide-range yeast vector (CoMed™) system to recombinant protein production in dimorphic Arxula adeninivorans, methylotrophic Hansenula polymorpha and other yeasts. Microbial Cell Factories, 5, 1–13.Google Scholar
  90. 90.
    Gnügge, R., & Rudolf, F. (2017). Saccharomyces cerevisiae Shuttle vectors. Yeast, 34, 205–221.Google Scholar
  91. 91.
    Chou, C.-C., Patel, M. T., & Gartenberg, M. R. (2015). A series of conditional shuttle vectors for targeted genomic integration in budding yeast. FEMS Yeast Research, 15, 1–9.Google Scholar
  92. 92.
    Hinnen, A., Buxton, F., Chaudhuri, B., Heim, J., Hottiger, T., Meyhack, B., & Pohlig, G. (1994). Gene expression in recombinant yeast. In A. Smith (Ed.), Gene expression in recombinant microorganisms (pp. 121–193). New York: Marcel Dekker.Google Scholar
  93. 93.
    Kojo, H., Greenberg, B. D., & Sugino, A. (1981). Yeast 2-micrometer plasmid DNA replication in vitro: Origin and direction. Proceedings of the National Academy of Sciences of the United States of America, 78, 7261–7265.Google Scholar
  94. 94.
    Gellissen, G., & Hollenberg, C. P. (1997). Application of yeasts in gene expression studies: A comparison of Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis-a review. Gene, 190, 87–97.Google Scholar
  95. 95.
    Klabunde, J., Kunze, G., Gellissen, G., & Hollenberg, C. P. (2003). Integration of heterologous genes in several yeast species using vectors containing a Hansenula polymorpha-derived rDNA-targeting element. FEMS Yeast Research, 4, 185–193.Google Scholar
  96. 96.
    Cregg, J. M., Barringer, K., Hessler, A., & Madden, K. (1985). Pichia pastoris as a host system for transformations. Molecular and Cellular Biology, 5, 3376–3385.Google Scholar
  97. 97.
    Degelmann, A., Müller, F., Sieber, H., Jenzelewski, V., Suckow, M., Strasser, A. W., & Gellissen, G. (2002). Strain and process development for the production of human cytokines in Hansenula polymorpha. FEMS Yeast Research, 2, 349–361.Google Scholar
  98. 98.
    Liu, Y., Li, Y., Liu, L., Hu, X., & Qiu, B. (2005). Design of vectors for efficient integration and transformation in Hansenula polymorpha. Biotechnology Letters, 27, 1529–1534.Google Scholar
  99. 99.
    Shen, M. W., Fang, F., Sandmeyer, S., & Da Silva, N. A. (2012). Development and characterization of a vector set with regulated promoters for systematic metabolic engineering in Saccharomyces cerevisiae. Yeast, 29, 495–503.Google Scholar
  100. 100.
    Machens, F., Balazadeh, S., Mueller-Roeber, B., & Messerschmidt, K. (2017). synthetic promoters and transcription factors for heterologous protein expression in Saccharomyces cerevisiae. Frontiers in Bioengineering and Biotechnology, 5, 1–11.Google Scholar
  101. 101.
    Vickers, C. E., Bydder, S. F., Zhou, Y., & Nielsen, L. K. (2013). Dual gene expression cassette vectors with antibiotic selection markers for engineering in Saccharomyces cerevisiae. Microbial Cell Factories, 12, 1–11.Google Scholar
  102. 102.
    Meurer, M., Chevyreva, V., Cerulus, B., & Knop, M. (2016). The regulatable MAL32 promoter in S. cerevisiae: Characteristics and tools. bioRxiv, 28, 1–18.Google Scholar
  103. 103.
    Nicaud, J.-M., Madzak, C., van den Broek, P., Gysler, C., Duboc, P., Niederberger, P., & Gaillardin, C. (2002). Protein expression and secretion in the yeast Yarrowia lipolytica. FEMS Yeast Research, 2, 371–379.Google Scholar
  104. 104.
    Juretzek, T., Dall, L., Mauersberger, M. T., Gaillardin, S., Barth, C., G. and Nicaud, J. M. (2001). Vectors for gene expression and amplification in the yeast Yarrowia lipolytica. Yeast, 18, 97–113.Google Scholar
  105. 105.
    Madzak, C., Tréton, B., & Blanchin-Roland, S. (2000). Strong hybrid promoters and integrative expression/secretion vectors for quasi-constitutive expression of heterologous proteins in the yeast Yarrowia lipolytica. Journal of Molecular Microbiology and Biotechnology, 2, 207–216.Google Scholar
  106. 106.
    Verbeke, J., Beopoulos, A., & Nicaud, J.-M. (2013). Efficient homologous recombination with short length flanking fragments in Ku70 deficient Yarrowia lipolytica strains. Biotechnology Letters, 35, 571–576.Google Scholar
  107. 107.
    Liu, L., Otoupal, P., Pan, A., & Alper, H. S. (2014). Increasing expression level and copy number of a Yarrowia lipolytica plasmid through regulated centromere function. FEMS Yeast Research, 14, 1124–1127.Google Scholar
  108. 108.
    Higgins, D. R., Busser, K., Comiskey, J., Whittier, P. S., Purcell, T. J., & Hoeffler, J. P. (1998) Small vectors for expression based on dominant drug resistance with direct multicopy selection. In D. R. Higgins & J. M. Cregg (Eds.), Pichia protocols, (pp. 41–53). New York: Springer.Google Scholar
  109. 109.
    Li, P., Anumanthan, A., Gao, X.-G., Ilangovan, K., Suzara, V. V., Düzgüneş, N., & Renugopalakrishnan, V. (2007). Expression of recombinant proteins in Pichia pastoris. Applied Biochemistry and Biotechnology, 142, 105–124.Google Scholar
  110. 110.
    Li, D., Zhang, B., Li, S., Zhou, J., Cao, H., Huang, Y., & Cui, Z. (2017). A novel vector for construction of markerless multicopy overexpression transformants in Pichia pastoris. Frontiers in Microbiology, 8, 1–12.Google Scholar
  111. 111.
    Kang, H. A., Sohn, J. H., Agaphonov, M. O., Choi, E. S., Ter-Avanesyan, M. D., & Rhee, S. K. (2002) Development of expression systems for the production of recombinant proteins in Hansenula polymorpha DL-1. In G. Gellissen (Ed.), Hansenula polymorpha: Biology and applications, (pp. 124–146). Hpboken: Wiley.Google Scholar
  112. 112.
    Agaphonov, M. O., Trushkina, P. M., Sohn, J., Choi, E., Rhee, S., & Ter-Avanesyan, M. D. (1999). Vectors for rapid selection of integrants with different plasmid copy numbers in the yeast Hansenula polymorpha DL1. Yeast, 15, 541–551.Google Scholar
  113. 113.
    Saraya, R., Krikken, A. M., Kiel, J. A., Baerends, R. J., Veenhuis, M., & van der Klei, I. J. (2012). Novel genetic tools for Hansenula polymorpha. FEMS Yeast Research, 12, 271–278.Google Scholar
  114. 114.
    Partow, S., Siewers, V., Bjørn, S., Nielsen, J., & Maury, J. (2010). Characterization of different promoters for designing a new expression vector in Saccharomyces cerevisiae. Yeast, 27, 955–964.Google Scholar
  115. 115.
    Blount, B. A., Weenink, T., Vasylechko, S., & Ellis, T. (2012). Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology. PLoS ONE, 7, 1–11.Google Scholar
  116. 116.
    Rantasalo, A., Czeizler, E., Virtanen, R., Rousu, J., Lähdesmäki, H., Penttilä, M., Jäntti, J., & Mojzita, D. (2016). Synthetic transcription amplifier system for orthogonal control of gene expression in Saccharomyces cerevisiae. PLoS ONE, 11, 1–19.Google Scholar
  117. 117.
    Öztürk, S., Ergün, B. G., & Çalık, P. (2017). Double promoter expression systems for recombinant protein production by industrial microorganisms. Applied Microbiology and Biotechnology, 101, 7459–7475.Google Scholar
  118. 118.
    Park, Y.-K., Korpys, P., Kubiak, M., Celińska, E., Soudier, P., Trébulle, P., Larroude, M., Rossignol, T., & Nicaud, J.-M. (2018). Engineering the architecture of erythritol-inducible promoters for regulated and enhanced gene expression in Yarrowia lipolytica. FEMS Yeast Research, 19, 1–32.Google Scholar
  119. 119.
    Larroude, M., Rossignol, T., Nicaud, J.-M., & Ledesma-Amaro, R. (2018). Synthetic biology tools for engineering Yarrowia lipolytica. Biotechnology Advances, 36, 2150–2164.Google Scholar
  120. 120.
    Çelik, E., Çalık, P., & Oliver, S. G. (2010). Metabolic flux analysis for recombinant protein production by Pichia pastoris using dual carbon sources: Effects of methanol feeding rate. Biotechnology and Bioengineering, 105, 317–329.Google Scholar
  121. 121.
    Arruda, A., Reis, V. C. B., Batista, V. D. F., Daher, B. S., Piva, L. C., De Marco, J. L., de Moraes, L. M. P., & Torres, F. A. G. (2016). A constitutive expression system for Pichia pastoris based on the PGK1 promoter. Biotechnology Letters, 38, 509–517.Google Scholar
  122. 122.
    Tschopp, J. F., Brust, P. F., Cregg, J. M., Stillman, C. A., & Gingeras, T. R. (1987). Expression of the lacZ gene from two methanol-regulated promoters in Pichia pastoris. Nucleic Acids Research, 15, 3859–3876.Google Scholar
  123. 123.
    Dusny, C., & Schmid, A. (2016). The MOX promoter in Hansenula polymorpha is ultrasensitive to glucose-mediated carbon catabolite repression. FEMS Yeast Research, 16, 1–15.Google Scholar
  124. 124.
    Suppi, S., Michelson, T., Viigand, K., & Alamäe, T. (2013). Repression vs. activation of MOX. FMD, MPP1 and MAL1 promoters by sugars in Hansenula polymorpha: The outcome depends on cell’s ability to phosphorylate sugar. FEMS Yeast Research, 13, 219–232.Google Scholar
  125. 125.
    Bae, J. H., Sohn, J. H., Rhee, S. K., & Choi, E. S. (2005). Cloning and characterization of the Hansenula polymorpha PEP4 gene encoding proteinase A. Yeast, 22, 13–19.Google Scholar
  126. 126.
    Heo, J.-H., Hong, W. K., Cho, E. Y., Kim, M. W., Kim, J.-Y., Kim, C. H., Rhee, S. K., & Kang, H. A. (2003). Properties of the Hansenula polymorpha-derived constitutive GAP promoter, assessed using an HSA reporter gene. FEMS Yeast Research, 4, 175–184.Google Scholar
  127. 127.
    Peng, B., Wood, R. J., Nielsen, L. K., & Vickers, C. E. (2018). An expanded heterologous GAL promoter collection for diauxie-inducible expression in Saccharomyces cerevisiae. ACS Synthetic Biology, 7, 748–751.Google Scholar
  128. 128.
    He, Y., Swaminathan, A., & Lopes, J. M. (2012). Transcription regulation of the Saccharomyces cerevisiae PHO5 gene by the Ino2p and Ino4p basic helix–loop–helix proteins. Molecular Microbiology, 83, 395–407.Google Scholar
  129. 129.
    Juretzek, T., Wang, H.-J., Nicaud, J.-M., Mauersberger, S., & Barth, G. (2000). Comparison of promoters suitable for regulated overexpression of β-galactosidase in the alkane-utilizing yeast Yarrowia lipolytica. Biotechnology and Bioprocess Engineering, 5, 320–326.Google Scholar
  130. 130.
    Hong, S. P., Seip, J., Walters-Pollak, D., Rupert, R., Jackson, R., Xue, Z., & Zhu, Q. (2012). Engineering Yarrowia lipolytica to express secretory invertase with strong FBA1IN promoter. Yeast, 29, 59–72.Google Scholar
  131. 131.
    Zeng, S. Y., Liu, H. H., Shi, T. Q., Song, P., Ren, L. J., Huang, H., & Ji, X. J. (2018). Recent advances in metabolic engineering of Yarrowia lipolytica for lipid overproduction. European Journal of Lipid Science and Technology, 120, 1–48.Google Scholar
  132. 132.
    Mellitzer, A., Ruth, C., Gustafsson, C., Welch, M., Birner-Grünberger, R., Weis, R., Purkarthofer, T., & Glieder, A. (2014). Synergistic modular promoter and gene optimization to push cellulase secretion by Pichia pastoris beyond existing benchmarks. Journal of Biotechnology, 191, 187–195.Google Scholar
  133. 133.
    Stadlmayr, G., Mecklenbräuker, A., Rothmüller, M., Maurer, M., Sauer, M., Mattanovich, D., & Gasser, B. (2010). Identification and characterisation of novel Pichia pastoris promoters for heterologous protein production. Journal of Biotechnology, 150, 519–529.Google Scholar
  134. 134.
    Liang, S., Zou, C., Lin, Y., Zhang, X., & Ye, Y. (2013). Identification and characterization of PGCW14: A novel, strong constitutive promoter of Pichia pastoris. Biotechnology Letters, 35, 1865–1871.Google Scholar
  135. 135.
    Capone, S., Horvat, J., Herwig, C., & Spadiut, O. (2015). Development of a mixed feed strategy for a recombinant Pichia pastoris strain producing with a de-repression promoter. Microbial Cell Factories, 14, 1–10.Google Scholar
  136. 136.
    Ruth, C., Zuellig, T., Mellitzer, A., Weis, R., Looser, V., Kovar, K., & Glieder, A. (2010). Variable production windows for porcine trypsinogen employing synthetic inducible promoter variants in Pichia pastoris. Systems and Synthetic Biology, 4, 181–191.Google Scholar
  137. 137.
    Wang, J., Wang, X., Shi, L., Qi, F., Zhang, P., Zhang, Y., Zhou, X., Song, Z., & Cai, M. (2017). Methanol-independent protein expression by AOX1 promoter with trans-acting elements engineering and glucose-glycerol-shift induction in Pichia pastoris. Scientific Reports, 7, 1–12.Google Scholar
  138. 138.
    Yang, M., Zhang, W., Ji, S., Cao, P., Chen, Y., & Zhao, X. (2013). Generation of an artificial double promoter for protein expression in Bacillus subtilis through a promoter trap system. PLoS ONE, 8, 1–9.Google Scholar
  139. 139.
    Nokelainen, M., Tu, H., Vuorela, A., Notbohm, H., Kivirikko, K. I., & Myllyharju, J. (2001). High-level production of human type I collagen in the yeast Pichia pastoris. Yeast, 18, 797–806.Google Scholar
  140. 140.
    Kamei, H., Ohira, T., Yoshiura, Y., Uchida, N., Nagasawa, H., & Aida, K. (2003). Expression of a biologically active recombinant follicle stimulating hormone of Japanese eel Anguilla japonica using methylotropic yeast, Pichia pastoris. General and Comparative Endocrinology, 134, 244–254.Google Scholar
  141. 141.
    Gasser, B., Saloheimo, M., Rinas, U., Dragosits, M., Rodríguez-Carmona, E., Baumann, K., Giuliani, M., Parrilli, E., Branduardi, P., & Lang, C. (2008). Protein folding and conformational stress in microbial cells producing recombinant proteins: A host comparative overview. Microbial Cell Factories, 7, 1–18.Google Scholar
  142. 142.
    Ata, Ö, Prielhofer, R., Gasser, B., Mattanovich, D., & Çalık, P. (2017). Transcriptional engineering of the glyceraldehyde-3-phosphate dehydrogenase promoter for improved heterologous protein production in Pichia pastoris. Biotechnology and Bioengineering, 114, 2319–2327.Google Scholar
  143. 143.
    Wagner, J. M., & Alper, H. S. (2016). Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances. Fungal Genetics and Biology, 89, 126–136.Google Scholar
  144. 144.
    Silvestrini, L., Rossi, B., Gallmetzer, A., Mathieu, M., Scazzocchio, C., Berardi, E., & Strauss, J. (2015). Interaction of Yna1 and Yna2 is required for nuclear accumulation and transcriptional activation of the nitrate assimilation pathway in the yeast Hansenula polymorpha. PLoS ONE, 10, 1–25.Google Scholar
  145. 145.
    Cox, H., Mead, D., Sudbery, P., Eland, R. M., Mannazzu, I., & Evans, L. (2000). Constitutive expression of recombinant proteins in the methylotrophic yeast Hansenula polymorpha using the PMA1 promoter. Yeast, 16, 1191–1203.Google Scholar
  146. 146.
    Stovicek, V., Holkenbrink, C., & Borodina, I. (2017). CRISPR/Cas system for yeast genome engineering: Advances and applications. FEMS Yeast Research, 17, 1–16.Google Scholar
  147. 147.
    Giersch, R. M., & Finnigan, G. C. (2017). Method for multiplexing CRISPR/Cas9 in Saccharomyces cerevisiae using artificial target DNA sequences. Bio-protocol, 7, 1–10.Google Scholar
  148. 148.
    Shi, T.-Q., Huang, H., Kerkhoven, E. J., & Ji, X.-J. (2018). Advancing metabolic engineering of Yarrowia lipolytica using the CRISPR/Cas system. Applied Microbiology and Biotechnology, 102, 9541–9548.Google Scholar
  149. 149.
    Löbs, A. K., Schwartz, C., & Wheeldon, I. (2017). Genome and metabolic engineering in non-conventional yeasts: Current advances and applications. Synthetic and Systems Biotechnology, 2, 198–207.Google Scholar
  150. 150.
    Baxter, M., Toms, G., Gadsby, R., & Griffiths, U. (2006). Empowering primary care practitioners to meet the growing challenge of diabetes care in the community. British Journal of Diabetes and Vascular Disease, 6, 245–248.Google Scholar
  151. 151.
    Bonander, N., & Bill, R. M. (2012) Optimising yeast as a host for recombinant protein production (review). In R. Bill (Ed.), Recombinant protein production in yeast (Vol. 866, pp. 1–9), New York: Springer.Google Scholar
  152. 152.
    Wang, T., Xu, Y., Liu, W., Sun, Y., & Jin, L. (2011). Expression of Apostichopus japonicus lysozyme in the methylotrophic yeast Pichia pastoris. Protein Expression and Purification, 77, 20–25.Google Scholar
  153. 153.
    Jahic, M., Gustavsson, M., Jansen, A.-K., Martinelle, M., & Enfors, S.-O. (2003). Analysis and control of proteolysis of a fusion protein in Pichia pastoris fed-batch processes. Journal of Biotechnology, 102, 45–53.Google Scholar
  154. 154.
    Mayson, B. E., Kilburn, D. G., Zamost, B. L., Raymond, C. K., & Lesnicki, G. J. (2003). Effects of methanol concentration on expression levels of recombinant protein in fed-batch cultures of Pichia methanolica. Biotechnology and Bioengineering, 81, 291–298.Google Scholar
  155. 155.
    Jungo, C., Marison, I., & von Stockar, U. (2007). Regulation of alcohol oxidase of a recombinant Pichia pastoris Mut+ strain in transient continuous cultures. Journal of Biotechnology, 130, 236–246.Google Scholar
  156. 156.
    Zhang, P., Zhang, W., Zhou, X., Bai, P., Cregg, J. M., & Zhang, Y. (2010). Catabolite repression of Aox in Pichia pastoris is dependent on hexose transporter PpHxt1 and pexophagy. Applied and Environmental Microbiology, 76, 6108–6118.Google Scholar
  157. 157.
    Arias, C. A. D., Marques, D. d. A. V., Malpiedi, L. P., Maranhão, A. Q., Parra, D. A. S., Converti, A., & Junior, A. P. (2017). Cultivation of Pichia pastoris carrying the scFv anti LDL (–) antibody fragment. Effect of preculture carbon source. Brazilian Journal of Microbiology, 4, 419–426.Google Scholar
  158. 158.
    Mahboubi, A., Mortazavi, S. A., Naghdi, N., & Azadi, S. (2017). Evaluation of sorbitol-methanol co-feeding strategy on production of recombinant human growth hormone in Pichia Pastoris. Iranian Journal of Pharmaceutical Research, 16, 1555–1564.Google Scholar
  159. 159.
    Trentmann, O., Khatri, N. K., & Hoffmann, F. (2004). Reduced oxygen supply increases process stability and product yield with recombinant Pichia pastoris. Biotechnology Progress, 20, 1766–1775.Google Scholar
  160. 160.
    Hellwig, S., Emde, F., Raven, N. P., Henke, M., van der Logt, P., & Fischer, R. (2001). Analysis of single-chain antibody production in Pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations. Biotechnology and Bioengineering, 74, 344–352.Google Scholar
  161. 161.
    Jazini, M., & Herwig, C. (2014). Two-compartment processing as a tool to boost recombinant protein production. Engineering in Life Sciences, 14, 118–128.Google Scholar
  162. 162.
    Jazini, M., Cekici, G., & Herwig, C. (2013). Quantifying the effects of frequency and amplitude of periodic oxygen-related stress on recombinant protein production in Pichia pastoris. Bioengineering, 1, 47–61.Google Scholar
  163. 163.
    Gasmi, N., Ayed, A., Ammar, B. B. H., Zrigui, R., Nicaud, J.-M., & Kallel, H. (2011). Development of a cultivation process for the enhancement of human interferon alpha 2b production in the oleaginous yeast, Yarrowia lipolytica. Microbial Cell Factories, 10, 90–100.Google Scholar
  164. 164.
    Ahmadzadeh, V., Farajnia, S., Feizi, M. A. H., & Nejad, R. A. K. (2014). Antibody humanization methods for development of therapeutic applications. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 33, 67–73.Google Scholar
  165. 165.
    Safdari, Y., Farajnia, S., Asgharzadeh, M., & Khalili, M. (2013). Antibody humanization methods–a review and update. Biotechnology and Genetic Engineering Reviews, 29, 175–186.Google Scholar
  166. 166.
    Dicker, M., & Strasser, R. (2015). Using glyco-engineering to produce therapeutic proteins. Expert Opinion on Biological Therapy, 15, 1501–1516.Google Scholar
  167. 167.
    Fidan, O., & Zhan, J. (2015). Recent advances in engineering yeast for pharmaceutical protein production. RSC Advances, 5, 86665–86674.Google Scholar
  168. 168.
    Jacobs, P. P., Geysens, S., Vervecken, W., Contreras, R., & Callewaert, N. (2008). Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nature Protocols, 4, 58–70.Google Scholar
  169. 169.
    He, T., Xu, S., Zhang, G., Nakanishi, H., & Gao, X. (2014). Reconstruction of N-glycosylation pathway for producing human glycoproteins in Saccharomyces cerevisiae. Wei sheng wu xue bao = Acta Microbiologica Sinica, 54, 509–516.Google Scholar
  170. 170.
    Khan, A. H., Bayat, H., Rajabibazl, M., Sabri, S., & Rahimpour, A. (2017). Humanizing glycosylation pathways in eukaryotic expression systems. World Journal of Microbiology and Biotechnology, 33, 1–12.Google Scholar
  171. 171.
    De Pourcq, K., Vervecken, W., Dewerte, I., Valevska, A., Van Hecke, A., & Callewaert, N. (2012). Engineering the yeast Yarrowia lipolytica for the production of therapeutic proteins homogeneously glycosylated with Man 8 GlcNAc 2 and Man 5 GlcNAc 2. Microbial Cell Factories, 11, 1–12.Google Scholar
  172. 172.
    Park, J.-N., Song, Y., Cheon, S. A., Kwon, O., Oh, D.-B., Jigami, Y., Kim, J.-Y., & Kang, H. A. (2011). Essential role of YlMPO1, a novel Yarrowia lipolytica homologue of Saccharomyces cerevisiae MNN4, in mannosylphosphorylation of N-and O-linked glycans. Applied and Environmental Microbiology, 77, 1187–1195.Google Scholar
  173. 173.
    Krainer, F. W., Gmeiner, C., Neutsch, L., Windwarder, M., Pletzenauer, R., Herwig, C., Altmann, F., Glieder, A., & Spadiut, O. (2013). Knockout of an endogenous mannosyltransferase increases the homogeneity of glycoproteins produced in Pichia pastoris. Scientific Reports, 3, 1–13.Google Scholar
  174. 174.
    Kunze, G., Kang, H. A., & Gellissen, G. (2009). Hansenula polymorpha (Pichia angusta): Biology and applications. In T. Satyanarayana & G. Kunze (Eds.), Yeast biotechnology: Diversity and applications (pp. 47–64). Dordrecht: Springer.Google Scholar
  175. 175.
    Huang, M., Bao, J., & Nielsen, J. (2014). Biopharmaceutical protein production by Saccharomyces cerevisiae: Current state and future prospects. Pharmaceutical Bioprocessing, 2, 167–182.Google Scholar
  176. 176.
    Huang, C.-J., Lowe, A. J., & Batt, C. A. (2010). Recombinant immunotherapeutics: Current state and perspectives regarding the feasibility and market. Applied Microbiology and Biotechnology, 87, 401–410.Google Scholar
  177. 177.
    Kannan, V., Narayanaswamy, P., Gadamsetty, D., Hazra, P., Khedkar, A., & Iyer, H. (2009). A tandem mass spectrometric approach to the identification of O-glycosylated glargine glycoforms in active pharmaceutical ingredient expressed in Pichia pastoris. European Journal of Lipid Science and Technology, 23, 1035–1042.Google Scholar
  178. 178.
    Shu, M., Shen, W., Wang, X., Wang, F., Ma, L., & Zhai, C. (2015). Expression, activation and characterization of porcine trypsin in Pichia pastoris GS115. Protein Expression and Purification, 114, 149–155.Google Scholar
  179. 179.
    Yang, H., Zhai, C., Yu, X., Li, Z., Tang, W., Liu, Y., Ma, X., Zhong, X., Li, G., & Wu, D. (2016). High-level expression of Proteinase K from Tritirachium album Limber in Pichia pastoris using multi-copy expression strains. Protein Expression and Purification, 122, 38–44.Google Scholar
  180. 180.
    Cicardi, M., Levy, R. J., McNeil, D. L., Li, H. H., Sheffer, A. L., Campion, M., Horn, P. T., & Pullman, W. E. (2010). Ecallantide for the treatment of acute attacks in hereditary angioedema. New England Journal of Medicine, 363, 523–531.Google Scholar
  181. 181.
    Tran, A.-M., Nguyen, T.-T., Nguyen, C.-T., Huynh-Thi, X.-M., Nguyen, C.-T., Trinh, M.-T., Tran, L.-T., Cartwright, S. P., Bill, R. M., & Tran-Van, H. (2017). Pichia pastoris versus Saccharomyces cerevisiae: A case study on the recombinant production of human granulocyte-macrophage colony-stimulating factor. BMC Research Notes, 10, 1–8.Google Scholar
  182. 182.
    Müller, I. I., Tieke, F., Waschk, A., Mühle, D., Müller, C., Seigelchifer, F., Pesce, M., Jenzelewski, A., V. and Gellissen, G. (2002). Production of IFNα-2 in Hansenula polymorpha. Process Biochemistry, 38, 15–25.Google Scholar
  183. 183.
    Matthäus, F., Ketelhot, M., Gatter, M., & Barth, G. (2014). Production of lycopene in the non-carotenoid-producing yeast Yarrowia lipolytica. Applied and Environmental Microbiology, 80, 1660–1669.Google Scholar
  184. 184.
    Blazeck, J., Hill, A., Liu, L., Knight, R., Miller, J., Pan, A., Otoupal, P., & Alper, H. S. (2014). Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nature Communications, 5, 1–10.Google Scholar
  185. 185.
    Yovkova, V., Otto, C., Aurich, A., Mauersberger, S., & Barth, G. (2014). Engineering the α-ketoglutarate overproduction from raw glycerol by overexpression of the genes encoding NADP+-dependent isocitrate dehydrogenase and pyruvate carboxylase in Yarrowia lipolytica. Applied Microbiology and Biotechnology, 98, 2003–2013.Google Scholar
  186. 186.
    Mirończuk, A. M., Furgała, J., Rakicka, M., & Rymowicz, W. (2014). Enhanced production of erythritol by Yarrowia lipolytica on glycerol in repeated batch cultures. Journal of Industrial Microbiology & Biotechnology, 41, 57–64.Google Scholar
  187. 187.
    Xue, Z., Sharpe, P. L., Hong, S.-P., Yadav, N. S., Xie, D., Short, D. R., Damude, H. G., Rupert, R. A., Seip, J. E., & Wang, J. (2013). Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica. Nature Biotechnology, 31, 734–740.Google Scholar
  188. 188.
    Harzevili, F. D. (2014) Yarrowia lipolytica in biotechnological applications. In D. Harzevili (Ed.), Biotechnological applications of the yeast Yarrowia lipolytica (pp. 17–74). Cham: Springer.Google Scholar
  189. 189.
    Domínguez, Á, Fermiñán, E., Sánchez, M., González, F. M., Pérez-Campo, F. M., García, S., Herrero, A. B., Vicente, S. A., Cabello, J., & Prado, M. (2010). Non-conventional yeasts as hosts for heterologous protein production. International Microbiology, 1, 131–142.Google Scholar
  190. 190.
    Safder, I., Khan, S., Islam, I., & Kazim, M. (2018). Pichia pastoris expression system: A potential candidate to express protein in industrial and biopharmaceutical domains. Biomedical Letters, 4, 1–13.Google Scholar
  191. 191.
    Andes, D., Craig, W., Nielsen, L., & Kristensen, H. (2009). In vivo pharmacodynamic characterization of a novel plectasin antibiotic, NZ2114, in a murine infection model. Antimicrobial Agents and Chemotherapy, 53, 3003–3009.Google Scholar
  192. 192.
    Mygind, P. H., Fischer, R. L., Schnorr, K. M., Hansen, M. T., Sönksen, C. P., Ludvigsen, S., Raventós, D., Buskov, S., Christensen, B., & De Maria, L. (2005). Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature., 437, 975–980.Google Scholar
  193. 193.
    Qian, W., Liu, Y., Zhang, C., Niu, Z., Song, H., & Qiu, B. (2009). Expression of bovine follicle-stimulating hormone subunits in a Hansenula polymorpha expression system increases the secretion and bioactivity in vivo. Protein Expression and Purification, 68, 183–189.Google Scholar
  194. 194.
    Ganeva, V., Galutzov, B., Angelova, B., & Suckow, M. (2018). Electroinduced extraction of human ferritin heavy chain expressed in Hansenula polymorpha. Applied Biochemistry and Biotechnology, 184, 1286–1307.Google Scholar
  195. 195.
    Wang, N., Wang, Y., Li, G., Sun, N., & Liu, D. (2011). Expression, characterization, and antimicrobial ability of t4 lysozyme from methylotrophic yeast hansenula polymorpha a16. Science China Life Sciences, 54, 520–526.Google Scholar
  196. 196.
    Cook, M., & Thygesen, H. (2003). Safety evaluation of a hexose oxidase expressed in Hansenula polymorpha. Food and Chemical Toxicology, 41, 523–529.Google Scholar
  197. 197.
    Gibson, D. G., Benders, G. A., Axelrod, K. C., Zaveri, J., Algire, M. A., Moodie, M., Montague, M. G., Venter, J. C., Smith, H. O., & Hutchison, C. A. (2008) One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome. Proceedings of the National Academy of Sciences of the United States of America, 105, 20404–20409.Google Scholar
  198. 198.
    Lartigue, C., Vashee, S., Algire, M. A., Chuang, R.-Y., Benders, G. A., Ma, L., Noskov, V. N., Denisova, E. A., Gibson, D. G., & Assad-Garcia, N. (2009). Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science, 325, 1693–1696.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Roghayyeh Baghban
    • 1
    • 2
    • 3
  • Safar Farajnia
    • 3
    • 4
    Email author
  • Masoumeh Rajabibazl
    • 5
    • 6
    Email author
  • Younes Ghasemi
    • 7
  • AmirAli Mafi
    • 8
  • Reyhaneh Hoseinpoor
    • 6
  • Leila Rahbarnia
    • 9
  • Maryam Aria
    • 3
  1. 1.Medical Biotechnology Department, Faculty of Advanced Medical ScienceTabriz University of Medical SciencesTabrizIran
  2. 2.Research CommitteeTabriz University of Medical SciencesTabrizIran
  3. 3.Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  5. 5.Department of Clinical Biochemistry, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran
  6. 6.Department of Biotechnology, School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  7. 7.Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterShiraz University of Medical ScienceShirazIran
  8. 8.Anesthesiology Research CenterShahid Beheshti University of Medical SciencesTehranIran
  9. 9.Infectious and Tropical Diseases Research CenterTabriz University of Medical SciencesTabrizIran

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