Skip to main content
SpringerLink
Log in

Kluyveromyces marxianus as a host for heterologous protein synthesis

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The preferentially respiring and thermotolerant yeast Kluyveromyces marxianus is an emerging host for heterologous protein synthesis, surpassing the traditional preferentially fermenting yeast Saccharomyces cerevisiae in some important aspects: K . marxianus can grow at temperatures 10 °C higher than S. cerevisiae, which may result in decreased costs for cooling bioreactors and reduced contamination risk; has ability to metabolize a wider variety of sugars, such as lactose and xylose; is the fastest growing eukaryote described so far; and does not require special cultivation techniques (such as fed-batch) to avoid fermentative metabolism. All these advantages exist together with a high secretory capacity, performance of eukaryotic post-translational modifications, and with a generally regarded as safe (GRAS) status. In the last years, replication origins from several Kluyveromyces spp. have been used for the construction of episomal vectors, and also integrative strategies have been developed based on the tendency for non-homologous recombination displayed by K. marxianus. The recessive URA3 auxotrophic marker and the dominant KanR are mostly used for selection of transformed cells, but other markers have been made available. Homologous and heterologous promoters and secretion signals have been characterized, with the K. marxianus INU1 expression and secretion system being of remarkable functionality. The efficient synthesis of roughly 50 heterologous proteins has been demonstrated, including one thermophilic enzyme. In this mini-review, we summarize the physiological characteristics of K. marxianus relevant for its use in the efficient synthesis of heterologous proteins, the efforts performed hitherto in the development of a molecular toolbox for this purpose, and some successful examples.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ballesteros M, Oliva JM, Negro MJ, Manzanares P, Ballesteros I (2004) Ethanol from lignocellulosic materials by a simultaneous saccharification and fermentation process (SFS) with Kluyveromyces marxianus CECT 10875. Process Biochem 39(12):1843–1848. doi:10.1016/j.procbio.2003.09.011

    Article  CAS  Google Scholar 

  • Belem MAF, Lee BH (1998) Production of bioingredients from Kluyveromyces marxianus grown on whey: an alternative. Crit Rev Food Sci Nutr 38:565–598. doi:10.1080/10408699891274318

    Article  CAS  PubMed  Google Scholar 

  • Bellaver LH, de Carvalho NM, Abrahão-Neto J, Gombert AK (2004) Ethanol formation and enzyme activities around glucose-6-phosphate in Kluyveromyces marxianus CBS 6556 exposed to glucose or lactose excess. FEMS Yeast Res 4:691–698. doi:10.1016/j.femsyr.2004.01.004

    Article  CAS  PubMed  Google Scholar 

  • Bergkamp RJM, Bootsman TC, Toschka HY, Mooren ATA, Kox L, Verbakel JMA, Geerse RH, Planta RJ (1993) Expression of an alpha-galactosidase gene under control of the homologous inulinase promoter in Kluyveromyces marxianus. Appl Microbiol Biotechnol 40:309–317. doi:10.1007/BF00170386

    Article  CAS  PubMed  Google Scholar 

  • Bragança CRS, Colombo LT, Roberti AS, Alvim MCT, Cardoso SA, Reis KCP, de Paula SO, da Silveira WB, Passos FML (2015) Construction of recombinant Kluyveromyces marxianus UFV-3 to express dengue virus type 1 nonstructural protein 1 (NS1). Appl Microbiol Biotechnol 99:1191–1203. doi:10.1007/s00253-014-5963-5

    Article  PubMed  Google Scholar 

  • Bruijne AW, Schuddemat J, van den Broek PJA, van Steveninck J (1988) Regulation of sugar transport systems of Kluyveromyces marxianus: the role of carbohydrates and their catabolism. Biochim Biophys Acta 939:569–576. doi:10.1016/0005-2736(88)90104-6

    Article  PubMed  Google Scholar 

  • Buckholz RG, Gleeson MAG (1991) Yeast systems for the commercial production of heterologous proteins. Bio/Technology 9:1067–1072. doi:10.1038/nbt1191-1067

    Article  CAS  PubMed  Google Scholar 

  • Castro RCA, Roberto IC (2014) Selection of a thermotolerant Kluyveromyces marxianus strain with potential application for cellulosic ethanol production by simultaneous saccharification and fermentation. Appl Biochem Biotechnol 172:1553–1564. doi:10.1007/s12010-013-0612-5

    Article  CAS  PubMed  Google Scholar 

  • Chang JJ, Ho CY, Ho FJ, Tsai TY, Ke HM, Wang CHT, Chen HL, Shih MC, Huang CC, Li WH (2012) PGASO: a synthetic biology tool for engineering a cellulolytic yeast. Biotechnol Biofuels 5:53. doi:10.1186/1754-6834-5-53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang JJ, Ho F, Ho C, Wu Y, Hou Y, Huang C, Shih M, Li W (2013) Assembling a cellulase cocktail and a cellodextrin transporter into a yeast host for CBP ethanol production. Biotechnol Biofuels 6:19. doi:10.1186/1754-6834-6-19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheon Y, Kim JS, Park JB, Heo P, Lim JH, Jung GY, Seo JH, Park JH, Koo HM, Cho KM, Park JB, Ha SJ, Kweon DH (2014) A biosynthetic pathway for hexanoic acid production in Kluyveromyces marxianus. J Biotechnol 182-183:30–36. doi:10.1016/j.jbiotec.2014.04.010

    Article  CAS  PubMed  Google Scholar 

  • Chen XJ (1996) Low- and high-copy-number shuttle vectors for replication in the budding yeast Kluyveromyces lactis. Gene 172:131–136. doi:10.1016/0378-1119(96)00125-4

    Article  CAS  PubMed  Google Scholar 

  • Choo JH, Han C, Kim JY, Kang HA (2014) Deletion of a KU80 homolog enhances homologous recombination in the thermotolerant yeast Kluyveromyces marxianus. Biotechnol Lett 36:2059–2067. doi:10.1007/s10529-014-1576-4

    Article  CAS  PubMed  Google Scholar 

  • De Deken RH (1966) The Crabtree effect: a regulatory system in yeast. Microbiology 44:149–156

    Google Scholar 

  • Delic M, Valli M, Graf AB, Pfeffer M, Mattanovich D, Gasser B (2013) The secretory pathway: exploring yeast diversity. FEMS Microbiol Rev 37:872–914

    Article  CAS  PubMed  Google Scholar 

  • Della-Bianca BE, Basso TO, Stambuk BU, Basso LC, Gombert AK (2013) What do we know about the yeast strains from the Brazilian fuel ethanol industry? Appl Microbiol Biotechnol 97:979–991. doi:10.1007/s00253-012-4631-x

    Article  CAS  PubMed  Google Scholar 

  • Diniz RHS, Silveira WB, Fietto LG, Passos FML (2012) The high fermentative metabolism of Kluyveromyces marxianus UFV-3 relies on the increased expression of key lactose metabolic enzymes. Antonie Van Leeuwenhoek 101:541–550. doi:10.1007/s10482-011-9668-9

    Article  CAS  PubMed  Google Scholar 

  • Dolashka-Angelova P, Moshtanska V, Kujumdzieva A, Atanasov B, Petrova V, Voelter W, Van Beeumen J (2010) Structure of glycosylated Cu/Zn-superoxide dismutase from Kluyveromyces yeast NBIMCC 1984. J Mol Struct 980:18–23

    Article  CAS  Google Scholar 

  • Domínguez A, Fermiñán E, Sánchez M, González FJ, Pérez-Campo FM, García S, Herrero AB, Vicente AS, Cabello J, Prado M, Iglesias FJ, Choupina A, Burguillo FJ, Fernández-Lago L, López MC (1998) Non-conventional yeasts as hosts for heterologous protein production. Int Microbiol 1:131–142. doi:10.1007/s00253-014-5948-4

    PubMed  Google Scholar 

  • Fonseca GG, de Carvalho NM, Gombert AK (2013) Growth of the yeast Kluyveromyces marxianus CBS 6556 on different sugar combinations as sole carbon and energy source. Appl Microbiol Biotechnol 97:5055–5067. doi:10.1007/s00253-013-4748-6

    Article  CAS  PubMed  Google Scholar 

  • Fonseca GG, Heinzle E, Wittmann C, Gombert AK (2008) The yeast Kluyveromyces marxianus and its biotechnological potential. Appl Microbiol Biotechnol 79:339–354. doi:10.1007/s00253-008-1458-6

    Article  CAS  PubMed  Google Scholar 

  • Fuciños P, Atanes E, López-López O, Cerdán ME, González-Siso MI, Pastrana L, Rúa ML (2011) Production and characterization of two N-terminal truncated esterases from Thermus thermophilus HB27 in a mesophilic yeast: effect of N-terminus in thermal activity and stability. Protein Expr Purif 78:120–130. doi:10.1016/j.pep.2011.04.002

    Article  PubMed  Google Scholar 

  • Gancedo JM (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62:334–361. doi:10.1111/j.1432-1033.1992.tb16928.x

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Y, Xu J, Yuan Z, Zhang Y, Liang C, Liu Y (2014) Ethanol production from high solids loading of alkali-pretreated sugarcane bagasse with an SSF process. Bioresources 9:3466–3479. doi:10.15376/biores.9.2.3466-3479

    Google Scholar 

  • Gasnier B (1987) Characterization of low- and high-affinity glucose transports in the yeast Kluyveromyces marxianus. Biochim Biophys Acta 903:425–433. doi:10.1016/0005-2736(87)90049-6

    Article  CAS  PubMed  Google Scholar 

  • Gemmill TR, Trimble RB (1999) Overview of N- and O-linked oligosaccharide structures found in various yeast species. Biochim Biophys Acta 1426:227–237. doi:10.1016/S0304-4165(98)00126-3

    Article  CAS  PubMed  Google Scholar 

  • González-Siso MI, Ramil E, Cerdán ME, Freire-Picos MA (1996) Respirofermentative metabolism in Kluyveromyces lactis: ethanol production and Crabtree effect. Enzym Microb Technol 18(8):585–591. doi:10.1016/0141-0229(95)00151-4

    Article  Google Scholar 

  • Goshima T, Negi K, Tsuji M, Inoue H, Yano S, Hoshino T, Matsushika A (2013a) Ethanol fermentation from xylose by metabolically engineered strains of Kluyveromyces marxianus. J Biosci Bioeng 116:551–554. doi:10.1016/j.jbiosc.2013.05.010

    Article  CAS  PubMed  Google Scholar 

  • Goshima T, Tsuji M, Inoue H, Yano S, Hoshino T, Matsushika A (2013b) Bioethanol production from lignocellulosic biomass by a novel Kluyveromyces marxianus strain. Biosci Biotechnol Biochem 77:1505–1010

    Article  CAS  PubMed  Google Scholar 

  • Groeneveld P, Stouthamer AH, Westerhoff HV (2009) Super life—how and why ‘cell selection’ leads to the fastest-growing eukaryote. FEBS J 276:254–270. doi:10.1111/j.1742-4658.2008.06778.x

    Article  CAS  PubMed  Google Scholar 

  • Hagman A, Säll T, Compagno C, Piskur J (2013) Yeast “Make-Accumulate-Consume” life strategy evolved as a multi-step process that predates the whole genome duplication. PLoS One 8(7):e68734. doi:10.1371/journal.pone.0068734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hensing MC, Rouwenhorst RJ, Heijnen JJ, van Dijken JP, Pronk JT (1995) Physiological and technological aspects of large-scale heterologous-protein production with yeasts. Antonie Van Leeuwenhoek 67:261–279. doi:10.1007/BF00873690

    Article  CAS  PubMed  Google Scholar 

  • Herrera T, Ulloa M, Fuentes I (1973) Descripción de una especie nueva de Hansenula y una variedad nueva de Candida parapsilosis aisladas del pozol. Bol Soc Mex Micol 7:17–26

    Google Scholar 

  • Hong J, Wang Y, Kumagai H, Tamaki H (2007) Construction of thermotolerant yeast expressing thermostable cellulase genes. J Biotechnol 130:114–123. doi:10.1016/j.jbiotec.2007.03.008

    Article  CAS  PubMed  Google Scholar 

  • Hoshida H, Murakami N, Suzuki A, Tamura R, Asakawa J, Abdel-Banat BMA, Nonklang S, Nakamura M, Akada R (2014) Non-homologous end joining-mediated functional marker selection for DNA cloning in the yeast Kluyveromyces marxianus. Yeast 31:29–46. doi:10.1002/yea.2993

    Article  CAS  PubMed  Google Scholar 

  • Inokuma K, Ishii J, Hara KY, Mochizuki M, Hasunuma T, Kondo A (2015) Complete genome sequence of Kluyveromyces marxianus strain NBRC1777, a nonconventional thermotolerant yeast. Genome Announc 3(2):e00389–e00315. doi:10.1128/genomeA.00389-15

    Article  PubMed  PubMed Central  Google Scholar 

  • Jakočiunas T, Jensen MK, Keasling JD (2016) CRISPR/Cas9 advances engineering of microbial cell factories. Metab Eng 34:44–59. doi:10.1016/j.ymben.2015.12.003

    Article  PubMed  Google Scholar 

  • Jeong H, Lee DH, Kim SH, Kim HJ, Lee K, Song JY, Kim BK, Sung BH, Park JC, Sohn JH, Koo HM, Kim JF (2012) Genome sequence of the thermotolerant yeast Kluyveromyces marxianus var. marxianus KCTC 17555. Eukaryot Cell 11:1584–1585. doi:10.1128/EC.00260-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kádár Z, Szengyel Z, Réczey K (2004) Simultaneous saccharification and fermentation (SSF) of industrial wastes for the production of ethanol. Ind Crop Prod 20:103–110. doi:10.1016/j.indcrop.2003.12.015

    Article  Google Scholar 

  • Kim TY, Lee SW, Oh MK (2014) Biosynthesis of 2-phenylethanol from glucose with genetically engineered Kluyveromyces marxianus. Enzym Microb Technol 61-62:44–47. doi:10.1016/j/enzmictec.2014.04.011

    Article  CAS  Google Scholar 

  • Kooistra R, Hooykaas PJJ, Steensma HY (2004) Efficient gene targeting in Kluyveromyces lactis. Yeast 21:81–792. doi:10.1002/yea.1131

    Article  Google Scholar 

  • Kurtzman CP (2003) Phylogenetic circumscription of Saccharomyces, Kluyveromyces and other members of the Saccharomycetaceae, and the proposal of the new genera Lachancea, Nakaseomyces, Naumovia, Vanderwaltozyma and Zygotorulaspora. FEMS Yeast Res 4:233–245

    Article  CAS  PubMed  Google Scholar 

  • Kurtzman CP, Fell JW, Boekhout T (2011) The yeasts: a taxonomic study, 5th edn. Elsevier, Amsterdam

    Google Scholar 

  • Lachance MA (2007) Current status of Kluyveromyces systematics. FEMS Yeast Res 7:642–645

    Article  CAS  PubMed  Google Scholar 

  • Lachance MA (2011) Kluyveromyces van der Walt (1971). In: Kurtzman CP, Fell JW, Boekhout T (2011) (eds) The yeasts: a taxonomic study, vol. 2, 5th edn. Elsevier. Amsterdam

  • Lane MM, Morrissey JP (2010) Kluyveromyces marxianus: a yeast emerging from its sister’s shadow. Fungal Biol Rev 24:17–26. doi:10.1016/j.fbr.2010.01.001

    Article  Google Scholar 

  • Laukens B, De Visscher C, Callewaert N (2015) Engineering yeast for producing human glycoproteins: where are we now? Future Microbiol 10(1):21–34. doi:10.2217/FMB.14.104

    Article  CAS  PubMed  Google Scholar 

  • Lee KS, Kim JS, Heo P, Yang TJ, Sung YJ, Cheon Y, Koo HM, Yu BJ, Seo JH, Jin YS, Park JC, Kweon DH (2013) Characterization of Saccharomyces cerevisiae promoters for heterologous gene expression in Kluyveromyces marxianus. Appl Microbiol Biotechnol 97:2029–2041. doi:10.1007/s00253-012-4306-7

    Article  CAS  PubMed  Google Scholar 

  • Lertwattanasakul N, Kosaka T, Hosoyama A, Suzuki Y, Rodrussamee N, Matsutani M, Murata M, Fujimoto N, Suprayogi TK, Limtong S, Fujita N, Yamada M (2015) Genetic basis of the highly efficient yeast Kluyveromyces marxianus: complete genome sequence and transcriptome analyses. Biotechnol Biofuels 8:47. doi:10.1186/s13068-015-0227-x

    Article  PubMed  PubMed Central  Google Scholar 

  • Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, Ballew N, Bobrowicz P, Choi B-K, Cook WJ, Cukan M, Houston-Cummings NR, Davidson R, Gong B, Hamilton SR, Hoopes JP, Jiang Y, Kim N, Mansfield R, Nett JH, Rios S, Strawbridge R, Wildt S, Gerngross TU (2006) Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol 24(2):210–215. doi:10.1038/nbt1178

    Article  CAS  PubMed  Google Scholar 

  • Ling KC (2008) Whey to ethanol: a biofuel role of dairy cooperatives? USDA Rural Development, Research Report 214 http://wwwrdusdagov/files/RR214pdf. Acessed 18 Feb 2016

  • Llorente B, Malpertuy A, Blandin G, Artiguenave F, Wincker P, Dujon B (2000) Genomic exploration of the hemiascomycetous yeasts: 12. Kluyveromyces marxianus var. marxianus. FEBS Lett 487:71–75

    Article  CAS  PubMed  Google Scholar 

  • López-López O, Fuciños P, Pastrana L, Rúa ML, Cerdán ME, González-Siso MI (2010) Heterologous expression of an esterase from Thermus thermophilus HB27 in Saccharomyces cerevisiae. J Biotechnol 145:226–232. doi:10.1016/j.jbiotec.2009.11.017

    Article  PubMed  Google Scholar 

  • López-López O, Cerdán ME, González-Siso MI (2015) Thermus thermophilus as a source of thermostable lipolytic enzymes. Microorganisms 3:792–808. doi:10.3390/microorganisms3040792

    Article  Google Scholar 

  • Löser C, Urit T, Bley T (2014) Perspectives for the biotechnological production of ethyl acetate by yeasts. Appl Microbiol Biotechnol 98:5397–5415. doi:10.1007/s00253-014-5765-9

    Article  PubMed  Google Scholar 

  • Matsuzaki C, Nakagawa A, Koyanagi T, Tanaka K, Minami H, Tamaki H, Katayama T, Yamamoto K, Kumagai H (2012) Kluyveromyces marxianus-based platform for direct ethanol fermentation and recovery from cellulosic materials under air-ventilated conditions. J Biosci Bioeng 113:604–607. doi:10.1016/j.jbiosc.2011.12.007

    Article  CAS  PubMed  Google Scholar 

  • Moreno AD, Ibarra D, Ballesteros I, González A, Ballesteros M (2013) Comparing cell viability and ethanol fermentation of the thermotolerant yeast Kluyveromyces marxianus and Saccharomyces cerevisiae on steam-exploded biomass treated with laccase. Bioresour Technol 135:239–245. doi:10.1016/j.biortech.2012.11.095

    Article  CAS  PubMed  Google Scholar 

  • Morrissey JP, Etschmann MM, Schrader J, de Billerbeck GM (2015) Cell factory applications of the yeast Kluyveromyces marxianus for the biotechnological production of natural flavour and fragrance molecules. Yeast 32:3–16. doi:10.1002/yea.3054

    CAS  PubMed  Google Scholar 

  • Nielsen J, Jewett MC (2008) Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae. FEMS Yeast Res 8:122–131. doi:10.1111/j.1567-1364.2007.00302.x

    Article  CAS  PubMed  Google Scholar 

  • Nielsen J, Keasling JD (2011) Synergies between synthetic biology and metabolic engineering. Nat Biotechnol 29:693–695. doi:10.1038/nbt.1937

    Article  CAS  PubMed  Google Scholar 

  • Nonklang S, Abdel-Banat BM, Cha-aim K, Moonjai N, Hoshida H, Limtong S, Yamada M, Akada R (2008) High-temperature ethanol fermentation and transformation with linear DNA in the thermotolerant yeast Kluyveromyces marxianus DMKU3-1042. Appl Environ Microbiol 74:7514–7521. doi:10.1128/AEM.01854-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nonklang S, Ano A, Abdel-Banat BMA, Saito Y, Hoshida H, Akada R (2009) Construction of flocculent Kluyveromyces marxianus strains suitable for high-temperature ethanol fermentation. Biosci Biotechnol Biochem 73:1090–1095. doi:10.1271/bbb.80853

    Article  CAS  PubMed  Google Scholar 

  • Pecota DC, Da Silva NA (2005) Evaluation of the tetracycline promoter system for regulated gene expression in Kluyveromyces marxianus. Biotechnol Bioeng 92:117–123. doi:10.1002/bit.20584

    Article  CAS  PubMed  Google Scholar 

  • Pecota DC, Rajgarhia V, Silva NA (2007) Sequential gene integration for the engineering of Kluyveromyces marxianus. J Biotechnol 127:408–416. doi:10.1016/j.jbiotec.2006.07.031

    Article  CAS  PubMed  Google Scholar 

  • Porro D, Sauer M, Branduardi P, Mattanovich D (2005) Recombinant protein production in yeasts. Mol Biotechnol 31:245–259. doi:10.1385/MB:31:3:245

    Article  CAS  PubMed  Google Scholar 

  • Postma E, Verduyn C, Scheffers WA, Van Dijken JP (1989) Enzymic analysis of the Crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microbiol 55(2):468–477

    CAS  PubMed  PubMed Central  Google Scholar 

  • Radecka D, Mukherjee V, Mateo RQ, Stojiljkovic M, Foulquié-Moreno MR, Thevelein JM (2015) Looking beyond Saccharomyces: the potential of non-conventional yeast species for desirable traits in bioethanol fermentation. FEMS Yeast Res 15(6):fov053

  • Raimondi S, Zanni E, Amaretti A, Palleschi C, Uccelletti D, Rossi M (2013) Thermal adaptability of Kluyveromyces marxianus in recombinant protein production. Microb Cell Factories 12:1–7. doi:10.1186/1475-2859-12-34

    Article  Google Scholar 

  • Raimondi S, Uccelletti D, Amaretti A, Leonardi A, Palleschi C, Rossi M (2010) Secretion of Kluyveromyces lactis Cu/Zn SOD: strategies for enhanced production. Appl Microbiol Biotechnol 86:871–878. doi:10.1007/s00253-009-2353-5

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro O, Gombert AK, Teixeira J, Domingues L (2007) Application of the cre-loxP system for multiple gene disruption in the yeast Kluyveromyces marxianus. J Biotechnol 131:20–26. doi:10.1016/j.jbiotec.2007.05.027

    Article  CAS  PubMed  Google Scholar 

  • Rocha SN, Abrahão-Neto J, Cerdán ME, Gombert AK, González-Siso MI (2011) Heterologous expression of a thermophilic esterase in Kluyveromyces yeasts. Appl Microbiol Biotechnol 89:375–385. doi:10.1007/s00253-010-2869-8

    Article  CAS  PubMed  Google Scholar 

  • Rocha SN, Abrahão-Neto J, Cerdán ME, González-Siso MI, Gombert AK (2010) Heterologous expression of glucose oxidase in the yeast Kluyveromyces marxianus. Microb Cell Factories 9:1–12. doi:10.1186/1475-2859-9-4

    Article  Google Scholar 

  • Romanos MA, Scorer CA, Clare JF (1992) Foreign gene expression in yeast: a review. Yeast 8:423–488. doi:10.1002/yea.320080602

    Article  CAS  PubMed  Google Scholar 

  • Rouwenhorst RJ, Visser LE, Van Der Baan AA, Scheffers WA, Van Dijken JP (1988) Production, distribution, and kinetic properties of inulinase in continuous cultures of Kluyveromyces marxianus CBS 6556. Appl Environ Microbiol 54:1131–1137

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sansonetti S, Hobley TJ, Curcio S, Villadsen J, Sin G (2013) Use of continuous lactose fermentation for ethanol production by Kluveromyces marxianus for verification and extension of a biochemically structured model. Bioresour Technol 130:703–709. doi:10.1016/j.biortech.2012.12.080

    Article  CAS  PubMed  Google Scholar 

  • Signori L, Passolunghi S, Ruohonen L, Porro D, Branduardi P (2014) Effect of oxygenation and temperature on glucose-xylose fermentation in Kluyveromyces marxianus CBS712 strain. Microb Cell Factories 13:51. doi:10.1186/1475-2859-13-51

    Article  Google Scholar 

  • Silveira W, Diniz RHS, Cerdán ME, González-Siso MI, Souza R, Vidigal P, Brustolini O, Prata EA, Medeiros A, Paiva L, Nascimento M, Ferreira E, Santos V, Bragança C, Fernandes T, Colombo L, Passos F (2014) Genomic sequence of the yeast Kluyveromyces marxianus CCT 7735 (UFV-3): a highly lactose fermenting yeast isolated from Brazilian dairy industry. Genome Announc 2:e01136–e01114. doi:10.1128/genomeA.01136-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Snoek ISI, Steensma HY (2006) Why does Kluyveromyces lactis not grow under anaerobic conditions? Comparison of essential anaerobic genes of Saccharomyces cerevisiae with the Kluyveromyces lactis genome. FEMS Yeast Res 6:393–403. doi:10.1111/j.1567-1364.2005.00007.x

    Article  CAS  PubMed  Google Scholar 

  • Solis-Escalante D, van den Broek M, Kuijpers NGA, Pronk JT, Boles E, Daran J-M, Daran-Lapujade P (2015) The genome sequence of the popular hexose-transport-deficient Saccharomyces cerevisiae strain EBY.VW4000 reveals LoxP/Cre-induced translocations and gene loss. FEMS Yeast Res 15(2):fou004. doi:10.1093/femsyr/fou004

    Article  PubMed  Google Scholar 

  • Souza CG Jr, MacDonald Ledingham W, Antônio De Morais M Jr (2001) Utilisation of cheese whey as an alternative growth medium for recombinant strains of Kluyveromyces marxianus. Biotechnol Lett 23:1413–1416. doi:10.1023/A:1011617914709

    Article  Google Scholar 

  • Stambuk BU, Franden MA, Singh A, Zhang M (2003) D-Xylose transport by Candida succiphila and Kluyveromyces marxianus. Appl Biochem Biotechnol 105-108:255–263. doi:10.1385/ABAB:106:1-3:255

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Hoshino T, Matsushika A (2014) Draft genome sequence of Kluyveromyces marxianus strain DMB1, isolated from sugarcane bagasse hydrolysate. Genome Announc 2(4):e00733–e00714. doi:10.1128/genomeA.00733-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Theron CW, Labuschagné M, Gudiminchi R, Albertyn J, Smit MS (2014) A broad-range yeast expression system reveals Arxula adeninivorans expressing a fungal self-sufficient cytochrome P450 monooxygenase as an excellent whole-cell biocatalyst. FEMS Yeast Res 14:556–566. doi:10.1111/1567-1364.12142

    Article  CAS  PubMed  Google Scholar 

  • van der Walt JP (1956) Kluyveromyces—a new yeast genus of the Endomycetales. Antonie Van Leeuwenhoek 22:265–272

    Article  Google Scholar 

  • van Ooyen AJ, Dekker P, Huang M, Olsthoorn MM, Jacobs DI, Colussi PA, Taron CH (2006) Heterologous protein production in the yeast Kluyveromyces lactis. FEMS Yeast Res 6:381–392

    Article  PubMed  Google Scholar 

  • Walker GM, O’Neill JD (1990) Morphological and metabolic changes in the yeast Kluyveromyces marxianus var. marxianus NRRLy2415 during fermentation of lactose. J Chem Technol Biotechnol 49:75–89. doi:10.1002/jctb.280490108

    Article  CAS  Google Scholar 

  • Wang YCM, Chuang LL, Lee FWF, Da Silva NA (2003) Sequential cloned gene integration in the yeast Kluyveromyces lactis. Appl Microbiol Biotechnol 62:523–527. doi:10.1007/s00253-003-1319-2

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Wang D, Gao X, Hong J (2014) Direct fermentation of raw starch using a Kluyveromyces marxianus strain that express glucoamylase and alpha-amylase to produce ethanol. Biotechnol Prog 30:338–347. doi:10.1002/btpr.1877

    Article  CAS  PubMed  Google Scholar 

  • WenJuan MO, Chao GUO, Hong LV (2014) Review of Kluyveromyces marxianus’ genetic and physiological features. Sci Sin Vitae. doi:10.1360/N052016-00101

    Google Scholar 

  • Wilkins MR, Mueller M, Eichling S, Banat IM (2008) Fermentation of xylose by the thermotolerant yeast strains Kluyveromyces marxianus IMB2, IMB4, and IMB5 under anaerobic conditions. Process Biochem 43:346–350. doi:10.1016/j.procbio.2007.12.011

    Article  CAS  Google Scholar 

  • Wolfe KH, Shields DC (1997) Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387(12):708–713

    Article  CAS  PubMed  Google Scholar 

  • Yanase S, Hasunuma T, Yamada R, Tanaka T, Ogino C, Fukuda H, Kondo A (2010) Direct ethanol production from cellulosic materials at high temperature using the thermotolerant yeast Kluyveromyces marxianus displaying cellulolytic enzymes. Appl Microbiol Biotechnol 88:381–388. doi:10.1007/s00253-010-2784-z

    Article  CAS  PubMed  Google Scholar 

  • Yang C, Hu S, Zhu S, Wang D, Gao X, Hong J (2015) Characterizing yeast promoters used in Kluyveromyces marxianus. World J Microbiol Biotechnol 31:1641–1646. doi:10.1007/s11274-015-1899-x

    Article  CAS  PubMed  Google Scholar 

  • Yarimizu T, Nakamura M, Hoshida H, Akada R (2015) Synthetic signal sequences that enable efficient secretory protein production in the yeast Kluyveromyces marxianus. Microb Cell Factories 14:20. doi:10.1186/s12934-015-0203-y

    Article  Google Scholar 

  • Yoshida Y, Naito E, Mizukoshi H, Watanabe Y, Kimura K, Yokoi W, Sato T, Okumura T, Ito M, Sawada H (2009) Side-chain structure of cell surface polysaccharide, mannan, affects hypocholesterolemic activity of yeast. J Agric Food Chem 57:8003–8009. doi:10.1021/jf900347q

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Zhang B, Wang D, Gao X, Hong J (2014) Xylitol production at high temperature by engineering Kluyveromyces marxianus. Bioresour Technol 152:192–201. doi:10.1016/j.biortech.2013.10.109

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Zhang B, Wang D, Gao X, Sun L, Hong J (2015) Rapid ethanol production at elevated temperatures by engineered thermotolerant Kluyveromyces marxianus via NADP(H)-preferring xylose reductase-xylitol dehydrogenase pathway. Metab Eng 31:140–152. doi:10.1016/j.ymben.2015.07.008

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

General support to the group EXPRELA was funded by Xunta de Galicia (Consolidación D.O.G. 10-10-2012. Contract Number: 2012/118) co-financed by FEDER. We also acknowledge support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil, through grant number 2015/14109-0. JVM-Jr. acknowledges a PNPD scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasília, Brazil.

Author information

Authors and Affiliations

  1. School of Food Engineering, University of Campinas, Rua Monteiro Lobato, 80, Campinas, SP, 13083-862, Brazil

    Andreas K. Gombert & José Valdo Madeira Jr.

  2. Grupo EXPRELA, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071, A Coruña, Spain

    María-Esperanza Cerdán & María-Isabel González-Siso

Authors
  1. Andreas K. Gombert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Valdo Madeira Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María-Esperanza Cerdán
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. María-Isabel González-Siso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María-Isabel González-Siso.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain studies with human participants or animals performed by any of the authors.

Additional information

Andreas K. Gombert and José Valdo Madeira Jr. contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gombert, A.K., Madeira, J.V., Cerdán, ME. et al. Kluyveromyces marxianus as a host for heterologous protein synthesis. Appl Microbiol Biotechnol 100, 6193–6208 (2016). https://doi.org/10.1007/s00253-016-7645-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-016-7645-y

Keywords

Search

Navigation