Skip to main content
SpringerLink
Log in

Functional analysis of Mpk1-mediated cell wall integrity signaling pathway in the thermotolerant methylotrophic yeast Hansenula polymorpha

  • Microbial Genetics, Genomics and Molecular Biology
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Understanding the characteristics and regulation mechanisms of cell wall integrity (CWI) in yeast is important not only for basic research but also in biotechnological applications. We found significantly different CWIs in two representative strains of the thermotolerant methylotrophic yeast Hansenula polymorpha. Compared to the A16 strain (classified as Ogataea polymorpha), the DL1-L strain (classified as Ogataea parapolymorpha) has a thinner cell wall that was found to be more fragile following long-term cultivation and more sensitive to zymolyase. To gain a deeper insight into this difference, we compared the characteristics of the Mpk1pmediated CWI signaling pathway in the two strains. While a DL1-L mutant deficient in Mpk1p (mpk1Δ) showed severe growth retardation at both normal and high growth temperatures and in the presence of cell-wall disrupting agents, the A16 mpk1Δ mutant displayed only a mild defect in cell growth. Sorbitol effect on rescuing growth retardation was different in the two mpk1Δ strains, which could partly be ascribed to subtle differences in the activation of HOG pathway. Among the cell wall disruptors evaluated, only caffeine clearly increased phosphorylation of Mpk1p in DL1-L, but not in A16. A transcriptome analysis of the DL1-L strain revealed that caffeine significantly increased the expression of a subset of cell-wall related genes in an Mpk1p-dependent manner, but not the expected Rlm1-target genes. Taken together, our data support an essential role for Mpk1p in maintaining CWI in H. polymorpha, although the requirement for Mpk1p and its regulation under diverse stress conditions varies depending on the strain background.

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

Similar content being viewed by others

References

  • Arana, D.M., Nombela, C., Alonso-Monge, R., and Pla, J. 2005. The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology 151, 1033–1049.

    Article  CAS  PubMed  Google Scholar 

  • Bermejo, C., Rodríguez, E., García, R., Rodríguez-Peña, J.M., Rodríguez de la Concepción, M.L., Rivas, C., Arias, P., Nombela, C., Posas, F., and Arroyo, J. 2008. The sequential activation of the yeast HOG and SLT2 pathways is required for cell survival to cell wall stress. Mol. Biol. Cell 19, 1113–1124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaffin, W.L. 2008. Candida albicans cell wall proteins. Microbiol. Mol. Biol. Rev. 72, 495–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, Y., Feldman, D.E., Deng, C., Brown, J.A., De Giacomo, A.F., Gaw, A.F., Shi, G., Le, Q.T., Brown, J.M., and Koong, A.C. 2005. Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol. Cancer Res. 3, 669–677.

    Article  CAS  PubMed  Google Scholar 

  • Chen, R.E. and Thorner, J. 2007. Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 1773, 1311–1340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, D., Toone, W.M., Mata, J., Lyne, R., Burns, G., Kivinen, K., Brazma, A., Jones, N., and Bahler, J. 2003. Global transcriptional responses of fission yeast to environmental stress. Mol. Biol. Cell 14, 214–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheon, S.A., Jung, K.W., Chen, Y.L., Heitman, J., Bahn, Y.S., and Kang, H.A. 2011. Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog. 7, e1002177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou, C.P. 2007. Engineering cell physiology to enhance recombinant protein production in Escherichia coli. Appl. Microbiol. Biotechnol. 76, 521–532.

    Article  CAS  PubMed  Google Scholar 

  • Cohen, R. and Engelberg, D. 2007. Commonly used Saccharomyces cerevisiae strains (e.g. BY4741, W303) are growth sensitive on synthetic complete medium due to poor leucine uptake. FEMS Microbiol. Lett. 273, 239–243.

    Article  CAS  PubMed  Google Scholar 

  • De Morais, J.O.F. and Maia, M.H.D. 1959. Estudos de microorganismos encontrados em leitos de despejos de caldas de destilarias de Pernambuco. II. Uma nova especie de Hansenula: H. poly morpha. Anais de Escola Superior de Quimica da Universidade do Recife 1, 15–20.

    Google Scholar 

  • Delgado-Silva, Y., Vaz, C., Carvalho-Pereira, J., Carneiro, C., Nogueira, E., Correia, A., Carreto, L., Silva, S., Faustino, A., Pais, C., et al. 2014. Participation of Candida albicans transcription factor RLM1 in cell wall biogenesis and virulence. PLoS One 9, e86270.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dichtl, K., Helmschrott, C., Dirr, F., and Wagener, J. 2012. Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases. Mol. Microbiol. 83, 506–519.

    Article  CAS  PubMed  Google Scholar 

  • Dmitruk, K.V. and Sibirnyi, A.A. 2013. Metabolic engineering of yeast Hansenula polymorpha for construction of efficient ethanol producers. TSitologiia i genetika 47, 3–21.

    CAS  PubMed  Google Scholar 

  • Donlin, M.J., Upadhya, R., Gerik, K.J., Lam, W., VanArendonk, L.G., Specht, C.A., Sharma, N.K., and Lodge, J.K. 2014. Cross talk between the cell wall integrity and cyclic AMP/protein kinase A pathways in Cryptococcus neoformans. mBio 5, e01573–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fuchs, B.B. and Mylonakis, E. 2009. Our paths might cross: the role of the fungal cell wall integrity pathway in stress response and cross talk with other stress response pathways. Eukaryot. Cell 8, 1616–1625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia, R., Rodriguez-Pena, J.M., Bermejo, C., Nombela, C., and Arroyo, J. 2009. The high osmotic response and cell wall integrity pathways cooperate to regulate transcriptional responses to zymolyase-induced cell wall stress in Saccharomyces cerevisiae. J. Biol. Chem. 284, 10901–10911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gellissen, G. 2006. Production of recombinant proteins: novel microbial and eukaryotic expression systems. Wiley-VCH, Germany.

    Google Scholar 

  • Gellissen, G., Kunze, G., Gaillardin, C., Cregg, J.M., Berardi, E., Veenhuis, M., and 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 Res. 5, 1079–1096.

    Article  CAS  PubMed  Google Scholar 

  • Hawle, P., Horst, D., Bebelman, J.P., Yang, X.X., Siderius, M., and van der Vies, S.M. 2007. Cdc37p is required for stress-induced highosmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p). Eukaryot. Cell 6, 521–532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawley, R.S. and Warburton, D. 2007. Scrambling eggs in plastic bottles. PLoS Genet. 3, e6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Heilmann, C.J., Sorgo, A.G., Mohammadi, S., Sosinska, G.J., de Koster, C.G., Brul, S., de Koning, L.J., and Klis, F.M. 2013. Surface stress induces a conserved cell wall stress response in the pathogenic fungus Candida albicans. Eukaryot. Cell 12, 254–264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heo, J.H., Hong, W.K., Cho, E.Y., Kim, M.W., Kim, J.Y., Kim, C.H., Rhee, S.K., and Kang, H.A. 2003. Properties of the Hansenula polymorpha-derived constitutive GAP promoter, assessed using an HSA reporter gene. FEMS Yeast Res. 4, 175–184.

    Article  CAS  PubMed  Google Scholar 

  • Hill, J., Donald, K.A., and Griffiths, D.E. 1991. DMSO-enhanced whole cell yeast transformation. Nucleic Acids Res. 19, 5791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hohmann, S., Krantz, M., and Nordlander, B. 2007. Yeast osmoregulation. Methods Enzymol. 428, 29–45.

    Article  CAS  PubMed  Google Scholar 

  • Ishchuk, O.P., Voronovsky, A.Y., Abbas, C.A., and Sibirny, A.A. 2009. Construction of Hansenula polymorpha strains with improved thermotolerance. Biotechnol. Bioeng. 104, 911–919.

    Article  CAS  PubMed  Google Scholar 

  • Jin, C. 2012. Protein glycosylation in Aspergillus fumigatus is essential for cell wall synthesis and serves as a promising model of multicellular eukaryotic development. Int. J. Microbiol. 2012, 654251.

    Article  PubMed  Google Scholar 

  • Jung, U.S. and Levin, D.E. 1999. Genome-wide analysis of gene expression regulated by the yeast cell wall integrity signalling pathway. Mol. Microbiol. 34, 1049–1057.

    Article  CAS  PubMed  Google Scholar 

  • Jung, U.S., Sobering, A.K., Romeo, M.J., and Levin, D.E. 2002. Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase. Mol. Microbiol. 46, 781–789.

    Article  CAS  PubMed  Google Scholar 

  • Kang, H.A., Sohn, J.H., Agaphonov, M.O., Choi, E.S., Ter-Avanesyan M.D., and Rhee, S.K. 2002. Hansenula polymorpha: Biology and Applications, pp. 124–146. In Gellissen, G. (ed.), Wiley-VCH, Weinheim, Germany.

  • Katz, S.J., Hofer, T.P., Hawley, S., Lantz, P.M., Janz, N.K., Schwartz, K., Liu, L., Deapen, D., and Morrow, M. 2007. Patterns and correlates of patient referral to surgeons for treatment of breast cancer. J. Clin. Oncol. 25, 271–276.

    Article  PubMed  Google Scholar 

  • Kim, M.W., Agaphonov, M.O., Kim, J.Y., Rhee, S.K., and Kang, H.A. 2002. Sequencing and functional analysis of the Hansenula polymorpha genomic fragment containing the YPT1 and PMI40 genes. Yeast 19, 863–871.

    Article  CAS  PubMed  Google Scholar 

  • Kim, K.Y., Cosano, I.C., Levin, D.E., Molina, M., and Martin, H. 2007. Dissecting the transcriptional activation function of the cell wall integrity MAP kinase. Yeast 24, 335–342.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.H., Han, K.Y., Lee, K., Heo, J.H., Kang, H.A., and Lee, J. 2004. Comparative proteome analysis of Hansenula polymorpha DL1 and A16. Proteomics 4, 2005–2013.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H., Moon, H.Y., Lee, D.J., Cheon, S.A., Yoo, S.J., Park, J.N., Agaphonov, M.O., Oh, D.B., Kwon, O., and Kang, H.A. 2013. Functional and molecular characterization of novel Hansenula polymorpha genes, HpPMT5 and HpPMT6, encoding protein O-mannosyltransferases. Fungal Genet. Biol. 58, 10–24.

    Article  PubMed  Google Scholar 

  • Kim, H., Thak, E.J., Lee, D.J., Agaphonov, M.O., and Kang, H.A. 2015. Hansenula polymorpha Pmt4p plays critical roles in O-mannosylation of surface membrane proteins and participates in heteromeric complex formation. PLoS One 10, e0129914.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim, H., Yoo, S.J., and Kang, H.A. 2015. Yeast synthetic biology for the production of recombinant therapeutic proteins. FEMS Yeast Res. 15, 1–16.

    Article  PubMed  Google Scholar 

  • Klis, F.M., Boorsma, A., and De Groot, P.W. 2006. Cell wall construction in Saccharomyces cerevisiae. Yeast 23, 185–202.

    Article  CAS  PubMed  Google Scholar 

  • Kraus, P.R., Fox, D.S., Cox, G.M., and Heitman, J. 2003. The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function. Mol. Microbiol. 48, 1377–1387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunze, G., Kang, H.A., and Gellissen, G. 2009 Hansenula polymorpha (Pichia angusta): biology and applications, pp. 47–64. In Satyanarayana, T. and Kunze, G. (eds.), Yeast Biotechnology: Diversity and Applications. Springer Science + Business Media B.V.

  • Kuranda, K., Leberre, V., Sokol, S., Palamarczyk, G., and Francois, J. 2006. Investigating the caffeine effects in the yeast Saccharomyces cerevisiae brings new insights into the connection between TOR, PKC and Ras/cAMP signalling pathways. Mol. Microbiol. 61, 1147–1166.

    Article  CAS  PubMed  Google Scholar 

  • Kurtzman, C.P. 2011. A new methanol assimilating yeast, Ogataea parapolymorpha, the ascosporic state of Candida parapolymorpha. Antonie van Leeuwenhoek 100, 455–462.

    Article  CAS  PubMed  Google Scholar 

  • Kurtzman, C.P. and Robnett, C.J. 2010. Systematics of methanol assimilating yeasts and neighboring taxa from multigene sequence analysis and the proposal of Peterozyma gen. nov., a new member of the Saccharomycetales. FEMS Yeast Res. 10, 353–361.

    Article  CAS  PubMed  Google Scholar 

  • Lee, K.S., Irie, K., Gotoh, Y., Watanabe, Y., Araki, H., Nishida, E., Matsumoto, K., and Levin, D.E. 1993. A yeast mitogen-activated protein-kinase homolog (mpk1p) mediates signaling by proteinkinase-c. Mol. Cell. Biol. 13, 3067–3075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lesage, G. and Bussey, H. 2006. Cell wall assembly in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 70, 317–343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levin, D.E. 2005. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 69, 262–291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levin, D.E. 2011. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics 189, 1145–1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine, D.W. and Cooney, C.L. 1973. Isolation and characterization of a thermotolerant methanol-utilizing yeast. Appl. Microbiol. 26, 982–990.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin, H., Rodriguez-Pachon, J.M., Ruiz, C., Nombela, C., and Molina, M. 2000. Regulatory mechanisms for modulation of sig naling through the cell integrity Slt2-mediated pathway in Saccharomyces cerevisiae. J. Biol. Chem. 275, 1511–1519.

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Lopez, R., Monteoliva, L., Diez-Orejas, R., Nombela, C., and Gil, C. 2004. The GPI-anchored protein CaEcm33p is required for cell wall integrity, morphogenesis and virulence in Candida albicans. Microbiology 150, 3341–3354.

    Article  CAS  PubMed  Google Scholar 

  • Monge, R.A., Roman, E., Nombela, C., and Pla, J. 2006. The MAP kinase signal transduction network in Candida albicans. Microbiology 152, 905–912.

    Article  CAS  PubMed  Google Scholar 

  • Mora-Montes, H.M. 2013. The fungal cell wall. Nova Science Publishers, Guanajuato, México.

    Google Scholar 

  • Navarro-Garcia, F., Sanchez, M., Pla, J., and Nombela, C. 1995. Functional characterization of the MKC1 gene of Candida albicans, which encodes a mitogen-activated protein kinase homolog related to cell integrity. J. Mol. Cell Biol. 15, 2197–2206.

    Article  CAS  Google Scholar 

  • Omara, W.A., Rash, B.M., Hayes, A., Wickham, M.S., Oliver, S.G., and Stateva, L.I. 2010. Conditional cell-wall mutants of Saccharomyces cerevisiae as delivery vehicles for therapeutic agents in vivo to the GI tract. J. Biotechnol. 147, 136–143.

    Article  CAS  PubMed  Google Scholar 

  • Popolo, L., Gualtieri, T., and Ragni, E. 2001. The yeast cell-wall salvage pathway. Med. Mycol. 39 Suppl 1, 111–121.

    Article  Google Scholar 

  • Ramezani-Rad, M., Hollenberg, C.P., Lauber, J., Wedler, H., Griess, E., Wagner, C., Albermann, K., Hani, J., Piontek, M., Dahlems, U., et al. 2003. The Hansenula polymorpha (strain CBS4732) genome sequencing and analysis. FEMS Yeast Res. 4, 207–215.

    Article  CAS  PubMed  Google Scholar 

  • 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., et al. 2013. Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1. BMC Genomics 14, 837.

    Article  PubMed  PubMed Central  Google Scholar 

  • Riley, R., Haridas, S., Wolfe, K.H., Lopes, M.R., Hittinger, C.T., Goker, M., Salamov, A.A., Wisecaver, J.H., Long, T.M., Calvey, C.H., et al. 2016. Comparative genomics of biotechnologically important yeasts. Proc. Natl. Acad. Sci. USA 113, 9882–9887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruepp, A., Zollner, A., Maier, D., Albermann, K., Hani, J., Mokrejs, M., Tetko, I., Guldener, U., Mannhaupt, G., Munsterkotter, M., et al. 2004. The funcat, a functional annotation scheme for systematic classification of proteins from whole genomes. Nucleic Acids Res. 32, 5539–5545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito, H. and Posas, F. 2012. Response to hyperosmotic stress. Genetics 192, 289–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh, S.L., Rai, R.C., Sah, S.K., and Komath, S.S. 2016. The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans. Yeast 33, 365–383.

    Article  CAS  PubMed  Google Scholar 

  • Soler, M., Plovins, A., Martin, H., Molina, M., and Nombela, C. 1995. Characterization of domains in the yeast MAP kinase Slt2 (Mpk1) required for functional activity and in vivo interaction with protein kinases Mkk1 and Mkk2. Mol. Microbiol. 17, 833–842.

    Article  CAS  PubMed  Google Scholar 

  • Suh, S.O. and Zhou, J.J. 2010. Methylotrophic yeasts near Ogataea (Hansenula) polymorpha: a proposal of Ogataea angusta comb. nov. and Candida parapolymorpha sp. nov. FEMS Yeast Res. 10, 631–638.

    CAS  PubMed  Google Scholar 

  • Swinnen, S., Goovaerts, A., Schaerlaekens, K., Dumortier, F., Verdyck, P., Souvereyns, K., Van Zeebroeck, G., Foulquie-Moreno, M.R., and Thevelein, J.M. 2015. Auxotrophic mutations reduce tolerance of Saccharomyces cerevisiae to very high levels of ethanol stress. Eukaryot. Cell 14, 884–897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tatjer, L., Sacristan-Reviriego, A., Casado, C., Gonzalez, A., Rodriguez- Porrata, B., Palacios, L., Canadell, D., Serra-Cardona, A., Martin, H., Molina, M., et al. 2016. Wide-ranging effects of the yeast Ptc1 protein phosphatase acting through the MAPK kinase Mkk1. Genetics 202, 141–156.

    Article  CAS  PubMed  Google Scholar 

  • Titz, B., Thomas, S., Rajagopala, S.V., Chiba, T., Ito, T., and Uetz, P. 2006. Transcriptional activators in yeast. Nucleic Acids Res. 34, 955–967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Truman, A.W., Kim, K.Y., and Levin, D.E. 2009. Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation. J. Mol. Cell Biol. 29, 6449–6461.

    Article  CAS  Google Scholar 

  • Valiante, V., Macheleidt, J., Foge, M., and Brakhage, A.A. 2015. The Aspergillus fumigatus cell wall integrity signaling pathway: drug target, compensatory pathways, and virulence. Front Microbiol. 6, 325.

    Article  PubMed  PubMed Central  Google Scholar 

  • van der Klei, I.J., Yurimoto, H., Sakai, Y., and Veenhuis, M. 2006. The significance of peroxisomes in methanol metabolism in methylotrophic yeast. Biochim. Biophys. Acta 1763, 1453–1462.

    Article  PubMed  Google Scholar 

  • Veale, R.A., Giuseppin, M.L., van Eijk, H.M., Sudbery, P.E., and Verrips, C.T. 1992. Development of a strain of Hansenula polymorpha for the efficient expression of guar a-galactosidase. Yeast 8, 361–372.

    Article  CAS  PubMed  Google Scholar 

  • Wickerham, L.J. 1951. Taxonomy of Yeasts. United States Department of Agriculture, Technical Bulletin No. 1029, Washington, D.C., USA.

    Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea

    Hyunah Kim, Eun Jung Thak, Ji Yoon Yeon, Min Jeong Sohn, Jin Ho Choo & Hyun Ah Kang

  2. Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea

    Jeong-Yoon Kim

Authors
  1. Hyunah Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eun Jung Thak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ji Yoon Yeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Jeong Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Ho Choo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeong-Yoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyun Ah Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jeong-Yoon Kim or Hyun Ah Kang.

Additional information

Supplemental material for this article may be found at http://www.springerlink.com/content/120956.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, H., Thak, E.J., Yeon, J.Y. et al. Functional analysis of Mpk1-mediated cell wall integrity signaling pathway in the thermotolerant methylotrophic yeast Hansenula polymorpha. J Microbiol. 56, 72–82 (2018). https://doi.org/10.1007/s12275-018-7508-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-018-7508-6

Keywords

Search

Navigation