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.
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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.
Han, M., & Yu, X. (2015). Enhanced expression of heterologous proteins in yeast cells via the modification of N-glycosylation sites. Bioengineered, 6, 115–118.
Nielsen, J. (2013). Production of biopharmaceutical proteins by yeast: Advances through metabolic engineering. Bioengineered, 4, 207–211.
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.
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.
Çelik, E., & Çalık, P. (2012). Production of recombinant proteins by yeast cells. Biotechnology Advances, 30, 1108–1118.
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.
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.
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.
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.
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.
Biddick, R., & Young, E. T. (2009). The disorderly study of ordered recruitment. Yeast, 26, 205–220.
Hohmann, S., Krantz, M., & Nordlander, B. (2007) Yeast osmoregulation. Methods in Enzymology, 428, 29–45.
Murakami, C., & Kaeberlein, M. (2009). Quantifying yeast chronological life span by outgrowth of aged cells. Journal of Visualized Experiments, 27, 1–4.
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.
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.
López-Mirabal, H. R., & Winther, J. R. (2008). Redox characteristics of the eukaryotic cytosol. Biochimica et Biophysica Acta Molecular Cell Research, 1783, 629–640.
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.
Munoz, A. J., Wanichthanarak, K., Meza, E., & Petranovic, D. (2012). Systems biology of yeast cell death. FEMS Yeast Research, 12, 249–265.
Miller-Fleming, L., Giorgini, F., & Outeiro, T. F. (2008). Yeast as a model for studying human neurodegenerative disorders. Biotechnology Journal, 3, 325–338.
Reggiori, F., & Klionsky, D. J. (2013). Autophagic processes in yeast: Mechanism, machinery and regulation. Genetics, 194, 341–361.
Karathia, H., Vilaprinyo, E., Sorribas, A., & Alves, R. (2011). Saccharomyces cerevisiae as a model organism: A comparative study. PLoS ONE, 6, 1–10.
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.
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.
Demain, A. L., & Vaishnav, P. (2009). Production of recombinant proteins by microbes and higher organisms. Biotechnology Advances, 27, 297–306.
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.
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.
Bekatorou, A., Psarianos, C., & Koutinas, A. A. (2006). Production of food grade yeasts. Food Technology and Biotechnology, 44, 407–415.
Mortimer, R. K., & Johnston, J. R. (1986). Genealogy of principal strains of the yeast genetic stock center. Genetics, 113, 35–43.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Madzak, C. (2015). Yarrowia lipolytica: Recent achievements in heterologous protein expression and pathway engineering. Applied Microbiology and Biotechnology, 99, 4559–4577.
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.
Zimmermann, R., Eyrisch, S., Ahmad, M., & Helms, V. (2011). Protein translocation across the ER membrane. Biochimica et Biophysica Acta, 1808, 912–924.
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.
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.
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.
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.
Schmidt, F. (2004). Recombinant expression systems in the pharmaceutical industry. Applied Microbiology and Biotechnology, 65, 363–372.
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.
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.
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.
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.
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.
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.
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.
Cregg, J. M., Cereghino, J. L., Shi, J., & Higgins, D. R. (2000). Recombinant protein expression in Pichia pastoris. Molecular Biotechnology, 16, 23–52.
Fickers, P. (2014). Pichia pastoris: A workhorse for recombinant protein production. Current Research in Microbiology and Biotechnology, 2, 354–363.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Gnügge, R., & Rudolf, F. (2017). Saccharomyces cerevisiae Shuttle vectors. Yeast, 34, 205–221.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Meurer, M., Chevyreva, V., Cerulus, B., & Knop, M. (2016). The regulatable MAL32 promoter in S. cerevisiae: Characteristics and tools. bioRxiv, 28, 1–18.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Larroude, M., Rossignol, T., Nicaud, J.-M., & Ledesma-Amaro, R. (2018). Synthetic biology tools for engineering Yarrowia lipolytica. Biotechnology Advances, 36, 2150–2164.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Stovicek, V., Holkenbrink, C., & Borodina, I. (2017). CRISPR/Cas system for yeast genome engineering: Advances and applications. FEMS Yeast Research, 17, 1–16.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Jazini, M., & Herwig, C. (2014). Two-compartment processing as a tool to boost recombinant protein production. Engineering in Life Sciences, 14, 118–128.
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.
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.
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.
Safdari, Y., Farajnia, S., Asgharzadeh, M., & Khalili, M. (2013). Antibody humanization methods–a review and update. Biotechnology and Genetic Engineering Reviews, 29, 175–186.
Dicker, M., & Strasser, R. (2015). Using glyco-engineering to produce therapeutic proteins. Expert Opinion on Biological Therapy, 15, 1501–1516.
Fidan, O., & Zhan, J. (2015). Recent advances in engineering yeast for pharmaceutical protein production. RSC Advances, 5, 86665–86674.
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.
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.
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.
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.
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.
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.
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.
Huang, M., Bao, J., & Nielsen, J. (2014). Biopharmaceutical protein production by Saccharomyces cerevisiae: Current state and future prospects. Pharmaceutical Bioprocessing, 2, 167–182.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Cook, M., & Thygesen, H. (2003). Safety evaluation of a hexose oxidase expressed in Hansenula polymorpha. Food and Chemical Toxicology, 41, 523–529.
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.
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.
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This study was supported by a Grant from the Biotechnology Research Center Tabriz University of Medical Science.
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Baghban, R., Farajnia, S., Rajabibazl, M. et al. Yeast Expression Systems: Overview and Recent Advances. Mol Biotechnol 61, 365–384 (2019). https://doi.org/10.1007/s12033-019-00164-8
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DOI: https://doi.org/10.1007/s12033-019-00164-8