Laboratory of Applied Stress MicrobiologyLaboratory of Applied Stress Microbiology

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Research Projects

1. Novel stress-tolerant mechanisms of yeast cells and their applications for breeding of industrial yeast

5) Development of industrial yeast based on novel stress-tolerant mechanisms

Through our basic research on the novel stress-tolerant mechanisms, we will construct industrial yeasts with higher tolerance to various stresses and contribute to yeast-based industry for the effective production of frozen dough and alcoholic beverages or the breakthrough of bioethanol production.

  1. H. T. Phuong, Y. Ishiwata-Kimata, Y. Nishi, N. Oguchi, H. Takagi and Y. Kimata: Aeration mitigates endoplasmic reticulum stress even without mitochondrial respiration in Saccharomyces cerevisiae. Microbial Cell, 8, 77-86 (2021).
  2. H. Takagi: Molecular mechanisms and highly-functional development for stress tolerance of the yeast Saccharomyces cerevisiae. Biosci. Biotech. Biochem., 85, 1017-1037 (2021). DOI: 10.1093/bbb/zbab022.
  3. Y. Nabilah Binti Mohd Fauzee, N. Taniguchi, Y. Ishiwata-Kimata, H. Takagi and Y. Kimata: The unfolded protein response in Pichia pastoris without external stressing stimuli. FEMS Yeast Res., 20, foaa053, in press. DOI: 10.1093/femsyr/foaa053.
  4. M. E. Prastya, R. I. Astuti, I. Batubara, H. Takagi and A. T. Wahyudi: Natural extract and its fractions isolated from the marine bacterium Pseudoalteromonas flavipulchra STILL-33 have antioxidant and antiaging activities in Schizosaccharomyces pombe. FEMS Yeast Res., 20, foaa014 (2020). DOI: 10.1093/femsyr/foaa014.
  5. M. E. Prastya, R. I. Astuti, I. Batubara, H. Takagi and A. T. Wahyudi: Chemical screening identifies an extract from marine Pseudomonas sp.-PTR-08 as an anti-aging agent that promotes fission yeast longevity by modulating the Pap1-ctt1+ pathway and the cell cycle. Mol. Biol. Rep., 47, 33-43 (2020).
  6. D. Watanabe, S. Tashiro, D. Shintani, Y. Sugimoto, A. Iwami, Y. Kajiwara, H. Takashita and H. Takagi: Loss of Rim15p in shochu yeast alters carbon utilization during barley shochu fermentation. Biosci. Biotech. Biochem., 83, 1594-1597 (2019).
  7. D. Watanabe, T. Kajihara, Y. Sugimoto, K. Takagi, M. Mizuno, Y. Zhou, J. Chen, K. Takeda, H. Tatebe, K. Shiozaki, N. Nakazawa, S. Izawa, T. Akao, H. Shimoi, T. Maeda and H. Takagi: Nutrient signaling via the TORC1-Greatwall-PP2AB55δ pathway responsible for the high Initial rates of alcoholic fermentation in sake yeast strains of Saccharomyces cerevisiae. Appl. Environ. Microbiol., 85(1), e02083-18 (2019).
  8. D. M. Tran, H. Takagi and Y. Kimata*: Categorization of endoplasmic reticulum stress as accumulation of unfolded proteins or membrane lipid aberrancy using yeast Ire1 mutants. Biosci. Biotech. Biochem., 83, 326-329 (2019).
  9. T. C. Mai, T. Munakata, D. M. Tran, H. Takagi and Y. Kimata*: A chimeric mutant analysis in yeast cells suggests BiP independent regulation of the mammalian endoplasmic reticulum-stress sensor IRE1α. Biosci. Biotech. Biochem., 82, 1527-1530 (2018).
  10. M. Oomuro, D. Watanabe, Y. Sugimoto, T. Kato, Y. Motoyama, T. Watanabe and H. Takagi: Accumulation of intracellular S-adenosylmethionine increases the fermentation rate of bottom-fermenting brewer's yeast during high-gravity brewing. J. Biosci. Bioeng., 126, 736-741 (2018).
  11. D. Watanabe, M. Kumano, Y. Sugimoto, M. Ito, M. Ohashi, K. Sunada, T. Takahashi, T. Yamada and H. Takagi: Metabolic switching of sake yeast by kimoto lactic acid bacteria through the [GAR+] non-genetic element. J. Biosci. Bioeng., 126, 624-629 (2018).
  12. D. A. Nur’utami, L. Haditjaroko, H. Takagi and K. Syamsu: Hyperosmotic stress tolerance of transcription activator Msn2-Over expression strain and proline-NO synthesis strain of Saccharomyces cerevisiae in very high gravity bioethanol fermentation. Pak. J. Biotechnol., 14, 135-139 (2017).
  13. D. Watanabe, H. Takagi: Pleiotropic functions of the yeast Greatwall-family protein kinase Rim15p: a novel target for the control of alcoholic fermentation. Biosci. Biotech. Biochem., 81, 1061-1068 (2017).
  14. D. Watanabe, A. Kaneko, Y. Sugimoto, T. Negishi, S. Ohnuki, H. Takagi and Y. Ohya: Promoter engineering of the Saccharomyces cerevisiae RIM15 gene for improvement of alcoholic fermentation rates under stress conditions. J. Biosci. Bioeng., 123, 183-189 (2017).
  15. D. Watanabe, Y. Zhou, A. Hirata, Y. Sugimoto, K. Takagi, T. Akao, Y. Ohya, H. Takagi and H. Shimoi*: Inhibitory role of Greatwall-like protein kinase Rim15p in alcoholic fermentation via upregulating the UDP-glucose synthesis pathway in Saccharomyces cerevisiae. Appl. Environ. Microbiol., 82, 340-351 (2016).
  16. S. Hirayama, M. Shimizu, N. Tsuchiya, S. Furukawa, D. Watanabe, H. Shimoi, H. Takagi, H. Ogihara and Y. Morinaga: Awa1p on the cell surface of sake yeast inhibits biofilm formation and the co-aggregation between sake yeasts and Lactobacillus plantarum ML11-11. J. Biosci. Bioeng., 119, 532-537 (2015).
  17. T. Inaba, D. Watanabe, Y. Yoshiyama, K. Tanaka, J. Ogawa, H. Takagi, H. Shimoi and J. Shima: An organic acid-tolerant HAA1-overexpression mutant of an industrial bioethanol strain of Saccharomyces cerevisiae and its application to the production of bioethanol from sugarcane molasses. AMB Express, 3:74, doi:10.1186/2191-0855-3-74 (2013).
  18. H. Kitagaki and H. Takagi: Mitochondrial metabolism and stress response of yeast: Applications in fermentation technologies. J. Biosci. Bioeng., 117, 383-393 (2013).
  19. Y. Sasano, Y. Haitani, K. Hashida, S. Oshiro, J. Shima and H. Takagi: Improvement of fermentation ability under baking-associated stress conditions by altering the POG1 gene expression in baker's yeast. Int. J. Food Microbiol., 165, 241-245 (2013).
  20. T. Inai, D. Watanabe, Y. Zhou, R. Fukada, T. Akao, J. Shima, H. Takagi and H. Shimoi: Rim15p-mediated regulation of sucrose utilization during molasses fermentation using Saccharomyces cerevisiae strain PE-2. J. Biosci. Bioeng., 116, 591-594 (2013).
  21. S. Hasegawa, T. Ogata, K. Tanaka, A. Ando, H. Takagi and J. Shima: Overexpression of vacuolar H+-ATPase-related genes in bottom-fermenting yeast enhances ethanol tolerance and fermentation rates during high-gravity fermentation. J. Inst. Brew., 118, 179-185 (2012).
  22. Y. Sasano*, Y. Haitani*, K. Hashida, I. Ohtsu, J. Shima and H. Takagi: Overexpression of the transcription activator Msn2 enhances fermentation ability of industrial baker’s yeast in frozen dough. *These authors contributed equally to this work. Biosci. Biotech. Biochem., 76, 624-627 (2012).
  23. Y. Sasano*, D. Watanabe*, K. Ukibe, T. Inai, I. Ohtsu, H. Shimoi and H. Takagi: Overexpression of the yeast transcription activator Msn2 confers furfural resistance and increases the initial fermentation rate in ethanol production. *These authors contributed equally to this work. J. Biosci. Bioeng., 113, 451-455 (2012).
  24. H. Urbanczyk, C. Noguchi, H. Wu, D. Watanabe, T. Akao, H. Takagi, H. Shimoi: Sake yeast strains have difficulty in entering a quiescent state after cell growth cessation. J. Biosci. Bioeng., 112, 44-48 (2011).
  25. T. Nakamura, S. Takahashi, H. Takagi and J. Shima: Multicopy suppression of oxidant-sensitive eos1 mutation by IZH2 in Saccharomyces cerevisiae and the involvement of Eos1 in zinc homeostasis. FEMS Yeast Res., 10, 259-269 (2010).
  26. K. Ukibe, K. Hashida, N. Yoshida and H. Takagi: Metabolic engineering of Saccharomyces cerevisiae for astaxanthin production and oxidative stress tolerance. Appl. Environ. Microbiol., 75, 7205-7211 (2009).
  27. S. Takahashi*, A. Ando*, H. Takagi and J. Shima: Insufficiency of copper ion homeostasis causes freeze-thaw injury of yeast cells revealed by indirect gene expression analysis. *These authors contributed equally to this work. Appl. Environ. Microbiol., 75, 6706-6711 (2009).
  28. J. Shima and H. Takagi: Stress-tolerance of baker’s yeast (Saccharomyces cerevisiae) cells: stress-protective molecules and genes involved in stress tolerance. Biotechnol. Appl. Biochem., 53, 155-164, 2009.
  29. H. Wu, T. Watanabe, Y. Araki, H. Kitagaki, T. Akao, H. Takagi and H. Shimoi: Disruption of ubiquitin-related genes in laboratory yeast strains enhances ethanol production during sake brewing. J. Biosci. Bioeng., 107, 636-640, 2009.
  30. T. Nakamura, H. Takagi and J. Shima: Effects of ice-seeding temperature and intracellular trehalose contents on survival of frozen Saccharomyces cerevisiae cells. Cryobiol., 58, 170-174 (2009).
  31. Y. Araki, H. Wu, H. Kitagaki, T. Akao, H. Takagi and H. Shimoi: Ethanol stress stimulates the Ca2+-mediated calcineurin/Crz1 pathway in Saccharomyces cerevisiae. J. Biosci. Bioeng., 107, 1-6 (2009).
  32. T. Nakamura, S. Mizukami-Murata, A. Ando, Y. Murata, H. Takagi and J. Shima: Changes in gene expression of commercial baker's yeast during an air-drying process that simulates dried yeast production. J. Biosci. Bioeng., 106, 405-408 (2008).
  33. J. Shima, A. Ando and H. Takagi: Possible roles of vacuolar H+-ATPase and mitochondrial function in tolerance to air-drying stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains. Yeast, 25, 179-190 (2008).
  34. F. Tanaka-Tsuno, S. Mizukami-Murata, Y. Murata, T. Nakamura, A. Ando, H. Takagi and J. Shima: Functional genomics of commercial baker’s yeasts that have different abilities for sugar utilization and high-sucrose tolerance under sugar conditions. Yeast, 24, 901-911 (2007).
  35. T. Nakamura, A. Ando, H. Takagi and J. Shima: Eos1, whose deletion confers sensitivity to oxidative stress, is involved in N-glycosylation in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 353, 293-298 (2007).
  36. A. Ando, T. Nakamura, Y. Murata, H. Takagi and J. Shima: Identification and classification of genes required for tolerance to freeze-thaw stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains. FEMS Yeast Res., 7, 244-253 (2007).
  37. H. Wu, X. Zheng, Y. Araki, H. Sahara, H. Takagi and H. Shimoi: Global gene expression analysis of yeast cells during sake brewing. Appl. Environ. Microbiol., 72, 7353-7358 (2006).
  38. F. Tanaka, A. Ando, T. Nakamura, H. Takagi and J. Shima: Functional genomic analysis of commercial baker’s yeast during initial stages of model dough-fermentation. Food Microbiology, 23, 717-728 (2006).
  39. M. Sugiura and H. Takagi: Yeast cell death caused by mutation of the OST2 gene encoding the -subunit of the Saccharomyces cerevisiae oligosaccharyltransferase. Biosci. Biotech. Biochem., 70, 1234-1241 (2006).
  40. A. Ando, F. Tanaka, Y. Murata, H. Takagi and J. Shima: Identification and classification of genes required for tolerance to high sucrose stress revealed by genome-wide screening of Saccharomyces cerevisiae. FEMS Yeast Research, 6, 249-267 (2006).
  41. M. Wada, S. Nakamori and H. Takagi: Serine racemase homologue of Saccharomyces cerevisiae has L-threo-3-hydroxyaspartate dehydratase activity. FEMS Microbiol. Lett., 225, 189-193 (2003).
  42. Y. Kubo, H. Takagi and S. Nakamori: Effect of gene disruption of succinate dehydrogenase on succinate production in a sake yeast strain. J. Biosci. Bioeng., 90, 619-624 (2000).