{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:40:59Z","timestamp":1785897659154,"version":"3.56.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"GteX Program of Japan","award":["JPMJGX23B4"],"award-info":[{"award-number":["JPMJGX23B4"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Microbiol Biotechnol"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Microbial production of valuable chemicals is a promising and sustainable approach, offering high energy efficiency and minimal waste generation. Production of 2,3-butanediol (2,3-BDO) by the safe industrial yeast\n                      <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                      holds potential as a sustainable bioprocess. However, the low tolerance of 2,3-BDO in yeast remains a major challenge. In this study, we aimed to improve 2,3-BDO tolerance in\n                      <jats:italic>S. cerevisiae<\/jats:italic>\n                      by introducing DNA point and structural mutations using techniques developed in previous studies, thereby advancing the sustainable industrial production of 2,3-BDO. Through point and structural mutagenesis, we successfully obtained the mutant strain YPH499\/Co58, which exhibited a 122-fold higher OD\n                      <jats:sub>600<\/jats:sub>\n                      value than the parent strain after 96\u00a0h of cultivation in a medium containing 175\u00a0g\/L 2,3-BDO. Transcriptome analysis of four mutants with particularly high 2,3-BDO tolerance suggested that the upregulation of genes related to the proteasome, peroxisome, TCA cycle, mitochondria, and transcriptional regulation was closely related to 2,3-BDO tolerance. The use of these mutant strains represents a major step toward realizing the sustainable industrial production of 2,3-BDO. Additionally, the insights gained in this study regarding 2,3-BDO tolerance may contribute to improving yeast tolerance to various stresses, including ethanol, heat, and low pH. The mutagenesis technique developed in this study holds promise for the construction of yeast strains with enhanced robustness for various applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>DNA point and structural mutations enhanced 2,3-BDO tolerance in yeast.<\/jats:italic>\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Engineered yeast mutant showed 122-fold higher growth in 175\u00a0g\/L 2,3-BDO.<\/jats:italic>\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Transcriptome analysis revealed key factors for 2,3-BDO tolerance.<\/jats:italic>\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-025-13626-8","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:32:38Z","timestamp":1760603558000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Construction of yeast with extremely high 2,3-butanediol tolerance by introducing point and structural mutations and partial elucidation of the mechanism of 2,3-butanediol tolerance"],"prefix":"10.1007","volume":"109","author":[{"given":"Kaito","family":"Nakamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3820-7501","authenticated-orcid":false,"given":"Ryosuke","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumi","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Ogino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"13626_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jbiosc.2009.03.019","volume":"108","author":"H Abe","year":"2009","unstructured":"Abe H, Fujita Y, Takaoka Y, Kurita E, Yano S, Tanaka N, Nakayama K (2009) Ethanol-tolerant Saccharomyces cerevisiae strains isolated under selective conditions by over-expression of a proofreading-deficient DNA polymerase delta. J Biosci Bioeng 108:199\u2013204. https:\/\/doi.org\/10.1016\/j.jbiosc.2009.03.019","journal-title":"J Biosci Bioeng"},{"key":"13626_CR2","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1128\/ec.00120-08","volume":"7","author":"B Annan Robert","year":"2008","unstructured":"Annan Robert B, Wu C, Waller Daniel D, Whiteway M, Thomas David Y (2008) Rho5p is involved in mediating the osmotic stress response in Saccharomyces cerevisiae, and its activity is regulated via Msi1p and Npr1p by phosphorylation and ubiquitination. Eukaryot Cell 7:1441\u20131449. https:\/\/doi.org\/10.1128\/ec.00120-08","journal-title":"Eukaryot Cell"},{"key":"13626_CR3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/s11274-016-2161-x","volume":"32","author":"AM Bia\u0142kowska","year":"2016","unstructured":"Bia\u0142kowska AM (2016) Strategies for efficient and economical 2,3-butanediol production: new trends in this field. World J Microbiol Biotechnol 32:200. https:\/\/doi.org\/10.1007\/s11274-016-2161-x","journal-title":"World J Microbiol Biotechnol"},{"key":"13626_CR4","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.femsyr.2004.10.010","volume":"5","author":"ZP Cakar","year":"2005","unstructured":"Cakar ZP, Seker UO, Tamerler C, Sonderegger M, Sauer U (2005) Evolutionary engineering of multiple-stress resistant Saccharomyces cerevisiae. FEMS Yeast Res 5:569\u2013578. https:\/\/doi.org\/10.1016\/j.femsyr.2004.10.010","journal-title":"FEMS Yeast Res"},{"key":"13626_CR5","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/yea.2948","volume":"30","author":"J Cao","year":"2013","unstructured":"Cao J, Barbosa JM, Singh NK, Locy RD (2013) Gaba shunt mediates thermotolerance in Saccharomyces cerevisiae by reducing reactive oxygen production. Yeast 30:129\u2013144. https:\/\/doi.org\/10.1002\/yea.2948","journal-title":"Yeast"},{"key":"13626_CR6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/bf00318659","volume":"21","author":"DC Chen","year":"1992","unstructured":"Chen DC, Yang BC, Kuo TT (1992) One-step transformation of yeast in stationary phase. Curr Genet 21:83\u201384. https:\/\/doi.org\/10.1007\/bf00318659","journal-title":"Curr Genet"},{"key":"13626_CR7","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foz055","volume":"19","author":"H Chen","year":"2019","unstructured":"Chen H, Li J, Wan C, Fang Q, Bai F, Zhao X (2019) Improvement of inhibitor tolerance in Saccharomyces cerevisiae by overexpression of the quinone oxidoreductase family gene YCR102C. FEMS Yeast Res 19:foz055. https:\/\/doi.org\/10.1093\/femsyr\/foz055","journal-title":"FEMS Yeast Res"},{"key":"13626_CR8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.freeradbiomed.2018.09.015","volume":"129","author":"JE Choi","year":"2018","unstructured":"Choi JE, Heo S-H, Kim MJ, Chung W-H (2018) Lack of superoxide dismutase in a rad51 mutant exacerbates genomic instability and oxidative stress-mediated cytotoxicity in Saccharomyces cerevisiae. Free Radic Biol Med 129:97\u2013106. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2018.09.015","journal-title":"Free Radic Biol Med"},{"key":"13626_CR9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/s12010-014-1006-z","volume":"174","author":"A Do\u011fan","year":"2014","unstructured":"Do\u011fan A, Demirci S, Aytekin A, \u015eahin F (2014) Improvements of tolerance to stress conditions by genetic engineering in Saccharomyces cerevisiae during ethanol production. Appl Biochem Biotechnol 174:28\u201342. https:\/\/doi.org\/10.1007\/s12010-014-1006-z","journal-title":"Appl Biochem Biotechnol"},{"key":"13626_CR10","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/0168-9525(96)10027-5","volume":"12","author":"B Dujon","year":"1996","unstructured":"Dujon B (1996) The yeast genome project: what did we learn? Trends Genet 12:263\u2013270. https:\/\/doi.org\/10.1016\/0168-9525(96)10027-5","journal-title":"Trends Genet"},{"key":"13626_CR11","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/nar\/30.2.581","volume":"30","author":"RT Elder","year":"2002","unstructured":"Elder RT, Song XQ, Chen M, Hopkins KM, Lieberman HB, Zhao Y (2002) Involvement of rhp23, a Schizosaccharomyces pombe homolog of the human HHR23A and Saccharomyces cerevisiae RAD23 nucleotide excision repair genes, in cell cycle control and protein ubiquitination. Nucleic Acids Res 30:581\u2013591. https:\/\/doi.org\/10.1093\/nar\/30.2.581","journal-title":"Nucleic Acids Res"},{"key":"13626_CR12","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1111\/j.1574-6976.2000.tb00553.x","volume":"24","author":"CL Flores","year":"2000","unstructured":"Flores CL, Rodr\u00edguez C, Petit T, Gancedo C (2000) Carbohydrate and energy-yielding metabolism in non-conventional yeasts. FEMS Microbiol Rev 24:507\u2013529. https:\/\/doi.org\/10.1111\/j.1574-6976.2000.tb00553.x","journal-title":"FEMS Microbiol Rev"},{"key":"13626_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103233","volume":"9","author":"D Greetham","year":"2014","unstructured":"Greetham D, Wimalasena TT, Leung K, Marvin ME, Chandelia Y, Hart AJ, Phister TG, Tucker GA, Louis EJ, Smart KA (2014) The genetic basis of variation in clean lineages of Saccharomyces cerevisiae in response to stresses encountered during bioethanol fermentations. PLoS ONE 9:e103233. https:\/\/doi.org\/10.1371\/journal.pone.0103233","journal-title":"PLoS ONE"},{"key":"13626_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-194","volume":"15","author":"N Hasin","year":"2014","unstructured":"Hasin N, Cusack SA, Ali SS, Fitzpatrick DA, Jones GW (2014) Global transcript and phenotypic analysis of yeast cells expressing Ssa1, Ssa2, Ssa3 or Ssa4 as sole source of cytosolic Hsp70-Ssa chaperone activity. BMC Genomics 15:194. https:\/\/doi.org\/10.1186\/1471-2164-15-194","journal-title":"BMC Genomics"},{"key":"13626_CR15","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/j.1460-2075.1991.tb07982.x","volume":"10","author":"W Heinemeyer","year":"1991","unstructured":"Heinemeyer W, Kleinschmidt JA, Saidowsky J, Escher C, Wolf DH (1991) Proteinase yscE, the yeast proteasome\/multicatalytic-multifunctional proteinase: mutants unravel its function in stress induced proteolysis and uncover its necessity for cell survival. EMBO J 10:555\u2013562","journal-title":"EMBO J"},{"key":"13626_CR16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12934-022-01924-z","volume":"21","author":"G Huo","year":"2022","unstructured":"Huo G, Foulqui\u00e9-Moreno MR, Thevelein JM (2022) Development of an industrial yeast strain for efficient production of 2,3-butanediol. Microb Cell Fact 21:199. https:\/\/doi.org\/10.1186\/s12934-022-01924-z","journal-title":"Microb Cell Fact"},{"key":"13626_CR17","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S0968-0004(96)20008-8","volume":"21","author":"MD Jacobson","year":"1996","unstructured":"Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends Biochem Sci 21:83\u201386. https:\/\/doi.org\/10.1016\/S0968-0004(96)20008-8","journal-title":"Trends Biochem Sci"},{"key":"13626_CR18","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.biotechadv.2011.01.007","volume":"29","author":"XJ Ji","year":"2011","unstructured":"Ji XJ, Huang H, Ouyang PK (2011) Microbial 2,3-butanediol production: a state-of-the-art review. Biotechnol Adv 29:351\u2013364. https:\/\/doi.org\/10.1016\/j.biotechadv.2011.01.007","journal-title":"Biotechnol Adv"},{"key":"13626_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s10529-024-03483-2","volume":"46","author":"Y Karitani","year":"2024","unstructured":"Karitani Y, Yamada R, Matsumoto T, Ogino H (2024) Improvement of cell growth in green algae Chlamydomonas reinhardtii through co-cultivation with yeast Saccharomyces cerevisiae. Biotechnol Lett 46:431\u2013441. https:\/\/doi.org\/10.1007\/s10529-024-03483-2","journal-title":"Biotechnol Lett"},{"key":"13626_CR20","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1002\/bit.22988","volume":"108","author":"KS Lee","year":"2011","unstructured":"Lee KS, Hong ME, Jung SC, Ha SJ, Yu BJ, Koo HM, Park SM, Seo JH, Kweon DH, Park JC, Jin YS (2011) Improved galactose fermentation of Saccharomyces cerevisiae through inverse metabolic engineering. Biotechnol Bioeng 108:621\u2013631. https:\/\/doi.org\/10.1002\/bit.22988","journal-title":"Biotechnol Bioeng"},{"key":"13626_CR21","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12934-021-01623-1","volume":"20","author":"NX Lin","year":"2021","unstructured":"Lin NX, He RZ, Xu Y, Yu XW (2021) Augmented peroxisomal ROS buffering capacity renders oxidative and thermal stress cross-tolerance in yeast. Microb Cell Fact 20:131. https:\/\/doi.org\/10.1186\/s12934-021-01623-1","journal-title":"Microb Cell Fact"},{"key":"13626_CR22","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s00253-010-2594-3","volume":"87","author":"M Ma","year":"2010","unstructured":"Ma M, Liu ZL (2010) Mechanisms of ethanol tolerance in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 87:829\u2013845","journal-title":"Appl Microbiol Biotechnol"},{"key":"13626_CR23","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00253-008-1732-7","volume":"82","author":"C Ma","year":"2009","unstructured":"Ma C, Wang A, Qin J, Li L, Ai X, Jiang T, Tang H, Xu P (2009) Enhanced 2,3-butanediol production by Klebsiella pneumoniae SDM. Appl Microbiol Biotechnol 82:49\u201357. https:\/\/doi.org\/10.1007\/s00253-008-1732-7","journal-title":"Appl Microbiol Biotechnol"},{"key":"13626_CR24","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1111\/mmi.13669","volume":"104","author":"S Manzanares-Estreder","year":"2017","unstructured":"Manzanares-Estreder S, Esp\u00ed-Bardisa J, Alarc\u00f3n B, Pascual-Ahuir A, Proft M (2017) Multilayered control of peroxisomal activity upon salt stress in Saccharomyces cerevisiae. Mol Microbiol 104:851\u2013868. https:\/\/doi.org\/10.1111\/mmi.13669","journal-title":"Mol Microbiol"},{"key":"13626_CR25","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1016\/j.jmb.2015.03.004","volume":"427","author":"M Mattiazzi U\u0161aj","year":"2015","unstructured":"Mattiazzi U\u0161aj M, Brlo\u017enik M, Kaferle P, \u017ditnik M, Wolinski H, Leitner F, Kohlwein SD, Zupan B, Petrovi\u010d U (2015) Genome-wide localization study of yeast Pex11 identifies peroxisome-mitochondria interactions through the ERMES complex. J Mol Biol 427:2072\u20132087. https:\/\/doi.org\/10.1016\/j.jmb.2015.03.004","journal-title":"J Mol Biol"},{"key":"13626_CR26","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1089\/omi.2010.0072","volume":"14","author":"NP Mira","year":"2010","unstructured":"Mira NP, Teixeira MC, S\u00e1-Correia I (2010) Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genome-wide view. OMICS 14:525\u2013540. https:\/\/doi.org\/10.1089\/omi.2010.0072","journal-title":"OMICS"},{"key":"13626_CR27","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1007\/s12010-019-03040-y","volume":"189","author":"R Mitsui","year":"2019","unstructured":"Mitsui R, Yamada R, Ogino H (2019) Improved stress tolerance of Saccharomyces cerevisiae by CRISPR-Cas-mediated genome evolution. Appl Biochem Biotechnol 189:810\u2013821. https:\/\/doi.org\/10.1007\/s12010-019-03040-y","journal-title":"Appl Biochem Biotechnol"},{"key":"13626_CR28","doi-asserted-by":"publisher","first-page":"9147","DOI":"10.1007\/s00253-020-10906-3","volume":"104","author":"R Mitsui","year":"2020","unstructured":"Mitsui R, Yamada R, Matsumoto T, Yoshihara S, Tokumoto H, Ogino H (2020) Construction of lactic acid-tolerant Saccharomyces cerevisiae by using CRISPR-Cas-mediated genome evolution for efficient D-lactic acid production. Appl Microbiol Biotechnol 104:9147\u20139158. https:\/\/doi.org\/10.1007\/s00253-020-10906-3","journal-title":"Appl Microbiol Biotechnol"},{"key":"13626_CR29","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s11274-021-03224-x","volume":"38","author":"R Mitsui","year":"2022","unstructured":"Mitsui R, Yamada R, Matsumoto T, Ogino H (2022) Bioengineering for the industrial production of 2,3-butanediol by the yeast, Saccharomyces cerevisiae. World J Microbiol Biotechnol 38:38. https:\/\/doi.org\/10.1007\/s11274-021-03224-x","journal-title":"World J Microbiol Biotechnol"},{"issue":"3","key":"13626_CR30","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jbiosc.2020.11.004","volume":"131","author":"A Mizobata","year":"2021","unstructured":"Mizobata A, Mitsui R, Yamada R, Matsumoto T, Yoshihara S, Tokumoto H, Ogino H (2021) Improvement of 2,3-butanediol tolerance in Saccharomyces cerevisiae by using a novel mutagenesis strategy. J Biosci Bioeng 131(3):283\u2013289. https:\/\/doi.org\/10.1016\/j.jbiosc.2020.11.004","journal-title":"J Biosci Bioeng"},{"key":"13626_CR31","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00294-014-0463-9","volume":"61","author":"N Nishida-Aoki","year":"2015","unstructured":"Nishida-Aoki N, Mori H, Kuroda K, Ueda M (2015) Activation of the mitochondrial signaling pathway in response to organic solvent stress in yeast. Curr Genet 61:153\u2013164. https:\/\/doi.org\/10.1007\/s00294-014-0463-9","journal-title":"Curr Genet"},{"key":"13626_CR32","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1128\/mmbr.64.1.34-50.2000","volume":"64","author":"S Ostergaard","year":"2000","unstructured":"Ostergaard S, Olsson L, Nielsen J (2000) Metabolic engineering of Saccharomyces cerevisiae. Microbiol Mol Biol Rev 64:34\u201350. https:\/\/doi.org\/10.1128\/mmbr.64.1.34-50.2000","journal-title":"Microbiol Mol Biol Rev"},{"key":"13626_CR33","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1128\/mmbr.63.2.349-404.1999","volume":"63","author":"F P\u00e2ques","year":"1999","unstructured":"P\u00e2ques F, Haber JE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63:349\u2013404. https:\/\/doi.org\/10.1128\/mmbr.63.2.349-404.1999","journal-title":"Microbiol Mol Biol Rev"},{"key":"13626_CR34","doi-asserted-by":"publisher","first-page":"13965","DOI":"10.1038\/s41598-022-18212-w","volume":"12","author":"HX Phong","year":"2022","unstructured":"Phong HX, Klanrit P, Dung NTP, Thanonkeo S, Yamada M, Thanonkeo P (2022) High-temperature ethanol fermentation from pineapple waste hydrolysate and gene expression analysis of thermotolerant yeast Saccharomyces cerevisiae. Sci Rep 12:13965. https:\/\/doi.org\/10.1038\/s41598-022-18212-w","journal-title":"Sci Rep"},{"key":"13626_CR35","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/860797","volume":"2012","author":"Y Shiwa","year":"2012","unstructured":"Shiwa Y, Fukushima-Tanaka S, Kasahara K, Horiuchi T, Yoshikawa H (2012) Whole-genome profiling of a novel mutagenesis technique using proofreading-deficient DNA polymerase \u03b4. Int J Evol Biol 2012:860797. https:\/\/doi.org\/10.1155\/2012\/860797","journal-title":"Int J Evol Biol"},{"key":"13626_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218097","volume":"21","author":"DS Spasskaya","year":"2020","unstructured":"Spasskaya DS, Nadolinskaia NI, Tutyaeva VV, Lysov YP, Karpov VL, Karpov DS (2020) Yeast Rpn4 links the proteasome and DNA repair via RAD52 regulation. Int J Mol Sci 21:8097. https:\/\/doi.org\/10.3390\/ijms21218097","journal-title":"Int J Mol Sci"},{"key":"13626_CR37","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s12192-016-0667-7","volume":"21","author":"A \u015awi\u0119ci\u0142o","year":"2016","unstructured":"\u015awi\u0119ci\u0142o A (2016) Cross-stress resistance in Saccharomyces cerevisiae yeast\u2013new insight into an old phenomenon. Cell Stress Chaperones 21:187\u2013200. https:\/\/doi.org\/10.1007\/s12192-016-0667-7","journal-title":"Cell Stress Chaperones"},{"key":"13626_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/fermentation10060318","volume":"10","author":"R Tanahashi","year":"2024","unstructured":"Tanahashi R, Nishimura A, Kan K, Ishizaki N, Fujishima S, Endo H, Takagi H (2024) Enhancing freezing stress tolerance through regulation of the ubiquitin\u2013proteasome system in Saccharomyces cerevisiae. Fermentation 10:318. https:\/\/doi.org\/10.3390\/fermentation10060318","journal-title":"Fermentation"},{"key":"13626_CR39","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.tibtech.2007.01.003","volume":"25","author":"KE Tyo","year":"2007","unstructured":"Tyo KE, Alper HS, Stephanopoulos GN (2007) Expanding the metabolic engineering toolbox: more options to engineer cells. Trends Biotechnol 25:132\u2013137. https:\/\/doi.org\/10.1016\/j.tibtech.2007.01.003","journal-title":"Trends Biotechnol"},{"key":"13626_CR40","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1021\/acsenergylett.9b02681","volume":"5","author":"K Xu","year":"2020","unstructured":"Xu K, Qin L, Bai W, Wang X, Li F, Ren S, Gao X, Chen B, Tong Y, Li J, Li B-Z, Yuan Y-J, Li C (2020) Multilevel Defense System (MDS) relieves multilevel defense system (MDS) relieves multiple stresses for economically boosting ethanol production of industrial Saccharomyces cerevisiae. ACS Energy Lett 5:572\u2013582. https:\/\/doi.org\/10.1021\/acsenergylett.9b02681","journal-title":"ACS Energy Lett"},{"key":"13626_CR41","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1016\/j.biortech.2017.05.034","volume":"245","author":"R Yamada","year":"2017","unstructured":"Yamada R, Wakita K, Mitsui R, Nishikawa R, Ogino H (2017) Efficient production of 2,3-butanediol by recombinant Saccharomyces cerevisiae through modulation of gene expression by cocktail delta-integration. Bioresour Technol 245:1558\u20131566. https:\/\/doi.org\/10.1016\/j.biortech.2017.05.034","journal-title":"Bioresour Technol"},{"key":"13626_CR42","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10295-018-2033-5","volume":"45","author":"R Yamada","year":"2018","unstructured":"Yamada R, Nishikawa R, Wakita K, Ogino H (2018) Rapid and stable production of 2,3-butanediol by an engineered Saccharomyces cerevisiae strain in a continuous airlift bioreactor. J Ind Microbiol Biotechnol 45:305\u2013311. https:\/\/doi.org\/10.1007\/s10295-018-2033-5","journal-title":"J Ind Microbiol Biotechnol"},{"key":"13626_CR43","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11274-020-02977-1","volume":"37","author":"R Yamada","year":"2021","unstructured":"Yamada R, Kumata Y, Mitsui R, Matsumoto T, Ogino H (2021) Improvement of lactic acid tolerance by cocktail \u03b4-integration strategy and identification of the transcription factor PDR3 responsible for lactic acid tolerance in yeast Saccharomyces cerevisiae. World J Microbiol Biotechnol 37:19. https:\/\/doi.org\/10.1007\/s11274-020-02977-1","journal-title":"World J Microbiol Biotechnol"},{"key":"13626_CR44","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1007\/s11274-024-04037-4","volume":"40","author":"R Yamada","year":"2024","unstructured":"Yamada R, Ando K, Sakaguchi R, Matsumoto T, Ogino H (2024) Induction of point and structural mutations in engineered yeast Saccharomyces cerevisiae improve carotenoid production. World J Microbiol Biotechnol 40:230. https:\/\/doi.org\/10.1007\/s11274-024-04037-4","journal-title":"World J Microbiol Biotechnol"},{"key":"13626_CR45","doi-asserted-by":"publisher","unstructured":"Yamada R, Inoue Y, Karitani Y, Sakaguchi R, Matsumoto T, Ogino H (2024b) Construction of high protein-producing mutant yeast strains via point and structural mutageneses and their use for carotenoid production. Res Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-5525851\/v1","DOI":"10.21203\/rs.3.rs-5525851\/v1"},{"key":"13626_CR46","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.biotechadv.2018.03.019","volume":"37","author":"Z Yang","year":"2019","unstructured":"Yang Z, Zhang Z (2019) Recent advances on production of 2, 3-butanediol using engineered microbes. Biotechnol Adv 37:569\u2013578. https:\/\/doi.org\/10.1016\/j.biotechadv.2018.03.019","journal-title":"Biotechnol Adv"},{"key":"13626_CR47","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523. https:\/\/doi.org\/10.1038\/s41467-019-09234-6","journal-title":"Nat Commun"}],"container-title":["Applied Microbiology and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-025-13626-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00253-025-13626-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-025-13626-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:33:14Z","timestamp":1770294794000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00253-025-13626-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["13626"],"URL":"https:\/\/doi.org\/10.1007\/s00253-025-13626-8","relation":{},"ISSN":["1432-0614"],"issn-type":[{"value":"1432-0614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]},"assertion":[{"value":"9 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants or animals performed by any authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"227"}}