{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:56:44Z","timestamp":1793912204287,"version":"4.8.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52300169"],"award-info":[{"award-number":["52300169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0108500"],"award-info":[{"award-number":["2022YFE0108500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microb Cell Fact"],"DOI":"10.1186\/s12934-025-02663-7","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T05:40:46Z","timestamp":1738215646000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Response mechanism of ethanol-tolerant Saccharomyces cerevisiae strain ES-42 to increased ethanol during continuous ethanol fermentation"],"prefix":"10.1186","volume":"24","author":[{"given":"Xue-Xue","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Xue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Ran","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Yong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Yun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Qin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"2663_CR1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.biotechadv.2007.09.002","volume":"26","author":"FW Bai","year":"2008","unstructured":"Bai FW, Anderson WA, Moo-Young M. Ethanol fermentation technologies from sugar and starch feedstocks. Biotechnol Adv. 2008;26:89\u2013105.","journal-title":"Biotechnol Adv"},{"key":"2663_CR2","first-page":"52","volume":"10","author":"SH Mohd Azhar","year":"2017","unstructured":"Mohd Azhar SH, Abdulla R, Jambo SA, Marbawi H, Gansau JA, Mohd Faik AA, et al. Yeasts in sustainable bioethanol production: a review. Biochem Biophys Rep. 2017;10:52\u201361.","journal-title":"Biochem Biophys Rep"},{"key":"2663_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2672.2009.04657.x","volume":"109","author":"D Stanley","year":"2010","unstructured":"Stanley D, Bandara A, Fraser S, Chambers PJ, Stanley GA. The ethanol stress response and ethanol tolerance of Saccharomyces cerevisiae. J Appl Microbiol. 2010;109:13\u201324.","journal-title":"J Appl Microbiol"},{"key":"2663_CR4","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.biotechadv.2009.05.013","volume":"27","author":"Y Shen","year":"2009","unstructured":"Shen Y, Zhao XQ, Ge XM, Bai FW. Metabolic flux and cell cycle analysis indicating new mechanism underlying process oscillation in continuous ethanol fermentation with Saccharomyces cerevisiae under VHG conditions. Biotechnol Adv. 2009;27:1118\u201323.","journal-title":"Biotechnol Adv"},{"key":"2663_CR5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/sj.jim.7000167","volume":"27","author":"DP Bayrock","year":"2001","unstructured":"Bayrock DP, Michael Ingledew W. Application of multistage continuous fermentation for production of fuel alcohol by very-high-gravity fermentation technology. J Ind Microbiol Biotechnol. 2001;27:87\u201393.","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2663_CR6","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1002\/bit.20221","volume":"88","author":"FW Bai","year":"2004","unstructured":"Bai FW, Chen LJ, Anderson WA, Moo-Young M. Parameter oscillations in a very high gravity medium continuous ethanol fermentation and their attenuation on a multistage packed column bioreactor system. Biotechnol Bioeng. 2004;88:558\u201366.","journal-title":"Biotechnol Bioeng"},{"key":"2663_CR7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jbiotec.2016.10.002","volume":"239","author":"A Thani","year":"2016","unstructured":"Thani A, Lin YH, Laopaiboon P, Laopaiboon L. Variation of fermentation redox potential during cell-recycling continuous ethanol operation. J Biotechnol. 2016;239:68\u201375.","journal-title":"J Biotechnol"},{"key":"2663_CR8","doi-asserted-by":"publisher","first-page":"7495","DOI":"10.1007\/s00253-020-10770-1","volume":"104","author":"C Liang","year":"2020","unstructured":"Liang C, Ding S, Sun W, Liu L, Zhao W, Zhang D, et al. Biofilm-based fermentation: a novel immobilisation strategy for Saccharomyces cerevisiae cell cycle progression during ethanol production. Appl Microbiol Biotechnol. 2020;104:7495\u2013505.","journal-title":"Appl Microbiol Biotechnol"},{"key":"2663_CR9","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1007\/s12155-020-10228-2","volume":"14","author":"U Jhariya","year":"2021","unstructured":"Jhariya U, Dafale NA, Srivastava S, Bhende RS, Kapley A, Purohit HJ. Understanding ethanol tolerance mechanism in to enhance the bioethanol production: current and future prospects. Bioenerg Res. 2021;14:670\u201388.","journal-title":"Bioenerg Res"},{"key":"2663_CR10","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ijfoodmicro.2006.02.002","volume":"110","author":"F Aguilera","year":"2006","unstructured":"Aguilera F, Peinado RA, Mill\u00e1n C, Ortega JM, Mauricio JC. Relationship between ethanol tolerance, H-ATPase activity and the lipid composition of the plasma membrane in different wine yeast strains. Int J Food Microbiol. 2006;110:34\u201342.","journal-title":"Int J Food Microbiol"},{"key":"2663_CR11","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1271\/bbb.68.968","volume":"68","author":"S Kubota","year":"2004","unstructured":"Kubota S, Takeo I, Kume K, Kanai M, Shitamukai A, Mizunuma M, et al. Effect of ethanol on cell growth of budding yeast: genes that are important for cell growth in the presence of ethanol. Biosci Biotechnol Biochem. 2004;68:968\u201372.","journal-title":"Biosci Biotechnol Biochem"},{"key":"2663_CR12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.copbio.2015.02.010","volume":"33","author":"JA Cray","year":"2015","unstructured":"Cray JA, Stevenson A, Ball P, Bankar SB, Eleutherio ECA, Ezeji TC, et al. Chaotropicity: a key factor in product tolerance of biofuel-producing microorganisms. Curr Opin Biotechnol. 2015;33:228\u201359.","journal-title":"Curr Opin Biotechnol"},{"key":"2663_CR13","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s00253-010-2594-3","volume":"87","author":"MG Ma","year":"2010","unstructured":"Ma MG, Liu ZL. Mechanisms of ethanol tolerance in Saccharomyces cerevisiae. Appl Microbiol Biotechnol. 2010;87:829\u201345.","journal-title":"Appl Microbiol Biotechnol"},{"key":"2663_CR14","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s00294-015-0561-3","volume":"62","author":"T Snoek","year":"2016","unstructured":"Snoek T, Verstrepen KJ, Voordeckers K. How do yeast cells become tolerant to high ethanol concentrations? Curr Genet. 2016;62:475\u201380.","journal-title":"Curr Genet"},{"key":"2663_CR15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s10295-009-0646-4","volume":"37","author":"BZ Li","year":"2010","unstructured":"Li BZ, Cheng JS, Qiao B, Yuan YJ. Genome-wide transcriptional analysis of Saccharomyces cerevisiae during industrial bioethanol fermentation. J Ind Microbiol Biotechnol. 2010;37:43\u201355.","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2663_CR16","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1002\/bit.27809","volume":"118","author":"X Zhang","year":"2021","unstructured":"Zhang X, Wang L, Li Q, den Haan R, Li F, Liu CG, et al. Omics analysis reveals mechanism underlying metabolic oscillation during continuous very-high-gravity ethanol fermentation by Saccharomyces cerevisiae. Biotechnol Bioeng. 2021;118:2990\u20133001.","journal-title":"Biotechnol Bioeng"},{"key":"2663_CR17","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.procbio.2020.12.022","volume":"102","author":"L Wang","year":"2021","unstructured":"Wang L, Li B, Wang SP, Xia ZY, Gou M, Tang YQ. Improving multiple stress-tolerance of a flocculating industrial Saccharomyces cerevisiae strain by random mutagenesis and hybridization. Process Biochem. 2021;102:275\u201385.","journal-title":"Process Biochem"},{"key":"2663_CR18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jbiotec.2017.03.030","volume":"251","author":"A Thani","year":"2017","unstructured":"Thani A, Laopaiboon P, Laopaiboon L. Improvement of a continuous ethanol fermentation from sweet sorghum stem juice using a cell recycling system. J Biotechnol. 2017;251:21\u20139.","journal-title":"J Biotechnol"},{"key":"2663_CR19","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13568-016-0218-8","volume":"6","author":"G Hernandez-Cortes","year":"2016","unstructured":"Hernandez-Cortes G, Valle-Rodriguez JO, Herrera-Lopez EJ, Diaz-Montano DM, Gonzalez-Garcia Y, Escalona-Buendia HB, et al. Improvement on the productivity of continuous tequila fermentation by Saccharomyces cerevisiae of Agave tequilana juice with supplementation of yeast extract and aeration. AMB Express. 2016;6:47.","journal-title":"AMB Express"},{"key":"2663_CR20","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s12934-022-01974-3","volume":"21","author":"YJ Wu","year":"2022","unstructured":"Wu YJ, Li B, Miao B, Xie CY, Tang YQ. Saccharomyces cerevisiae employs complex regulation strategies to tolerate low pH stress during ethanol production. Microb Cell Fact. 2022;21:247.","journal-title":"Microb Cell Fact"},{"key":"2663_CR21","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.","journal-title":"BMC Bioinformatics"},{"key":"2663_CR22","doi-asserted-by":"publisher","first-page":"107540","DOI":"10.1016\/j.ypmed.2023.107540","volume":"172","author":"XM Gao","year":"2023","unstructured":"Gao XM, Zhou XH, Jia MW, Wang XZ, Liu D. Identification of key genes in sepsis by WGCNA. Prev Med. 2023;172:107540.","journal-title":"Prev Med"},{"key":"2663_CR23","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, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.","journal-title":"Nat Commun"},{"key":"2663_CR24","doi-asserted-by":"crossref","unstructured":"Lopez Sanchez MIG, Kruger A, Shiriaev DI, Liu Y, Rorbach J. Human mitoribosome biogenesis and its emerging links to disease. Int J Mol Sci. 2021;22.","DOI":"10.3390\/ijms22083827"},{"key":"2663_CR25","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41586-022-05621-0","volume":"614","author":"NJ Harper","year":"2023","unstructured":"Harper NJ, Burnside C, Klinge S. Principles of mitoribosomal small subunit assembly in eukaryotes. Nature. 2023;614:175\u201381.","journal-title":"Nature"},{"key":"2663_CR26","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1128\/AEM.04151-13","volume":"80","author":"CM Henderson","year":"2014","unstructured":"Henderson CM, Block DE. Examining the role of membrane lipid composition in determining the ethanol tolerance of Saccharomyces cerevisiae. Appl Environ Microbiol. 2014;80:2966\u201372.","journal-title":"Appl Environ Microbiol"},{"key":"2663_CR27","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1515\/hsz-2016-0277","volume":"398","author":"S Ballweg","year":"2017","unstructured":"Ballweg S, Ernst R. Control of membrane fluidity: the OLE pathway in focus. Biol Chem. 2017;398:215\u201328.","journal-title":"Biol Chem"},{"key":"2663_CR28","doi-asserted-by":"crossref","unstructured":"Yang YJ, Xia YJ, Hu WY, Tao LR, Ni L, Yu JS et al. Membrane fluidity of Saccharomyces cerevisiae from Huangjiu (Chinese rice wine) is variably regulated by OLE1 to offset the disruptive effect of ethanol. Appl Environ Microbiol. 2019;85.","DOI":"10.1128\/AEM.01620-19"},{"key":"2663_CR29","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s10529-010-0465-8","volume":"33","author":"HS Kim","year":"2011","unstructured":"Kim HS, Kim NR, Choi W. Total fatty acid content of the plasma membrane of Saccharomyces cerevisiae is more responsible for ethanol tolerance than the degree of unsaturation. Biotechnol Lett. 2011;33:509\u201315.","journal-title":"Biotechnol Lett"},{"key":"2663_CR30","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s12088-017-0657-1","volume":"57","author":"ZH Hu","year":"2017","unstructured":"Hu ZH, He B, Ma L, Sun YL, Niu YL, Zeng B. Recent advances in ergosterol biosynthesis and regulation mechanisms in Saccharomyces cerevisiae. Indian J Microbiol. 2017;57:270\u20137.","journal-title":"Indian J Microbiol"},{"key":"2663_CR31","doi-asserted-by":"crossref","unstructured":"Gossing M, Smialowska A, Nielsen J. Impact of forced fatty acid synthesis on metabolism and physiology of Saccharomyces cerevisiae. FEMS Yeast Res. 2018;18.","DOI":"10.1093\/femsyr\/foy096"},{"key":"2663_CR32","doi-asserted-by":"crossref","unstructured":"Mirisola MG, Longo VD. Yeast chronological lifespan: longevity regulatory genes and mechanisms. Cells. 2022;11.","DOI":"10.3390\/cells11101714"},{"key":"2663_CR33","doi-asserted-by":"publisher","first-page":"e1000467","DOI":"10.1371\/journal.pgen.1000467","volume":"5","author":"M Wei","year":"2009","unstructured":"Wei M, Fabrizio P, Madia F, Hu J, Ge H, Li LM, et al. Tor1\/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension. PLoS Genet. 2009;5:e1000467.","journal-title":"PLoS Genet"},{"key":"2663_CR34","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s11274-017-2376-5","volume":"33","author":"R Li","year":"2017","unstructured":"Li R, Xiong G, Yuan S, Wu Z, Miao Y, Weng P. Investigating the underlying mechanism of Saccharomyces cerevisiae in response to ethanol stress employing RNA-seq analysis. World J Microbiol Biotechnol. 2017;33:206.","journal-title":"World J Microbiol Biotechnol"},{"key":"2663_CR35","doi-asserted-by":"publisher","first-page":"103377","DOI":"10.1016\/j.jprot.2019.103377","volume":"203","author":"R Li","year":"2019","unstructured":"Li R, Miao Y, Yuan S, Li Y, Wu Z, Weng P. Integrated transcriptomic and proteomic analysis of the ethanol stress response in Saccharomyces cerevisiae Sc131. J Proteom. 2019;203:103377.","journal-title":"J Proteom"},{"key":"2663_CR36","doi-asserted-by":"crossref","unstructured":"Ando R, Ishikawa Y, Kamada Y, Izawa S. Contribution of the yeast bi-chaperone system in the restoration of the RNA helicase Ded1 and translational activity under severe ethanol stress. J Biol Chem. 2023;299.","DOI":"10.1016\/j.jbc.2023.105472"},{"key":"2663_CR37","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.bpj.2011.12.038","volume":"102","author":"JM Vanegas","year":"2012","unstructured":"Vanegas JM, Contreras MF, Faller R, Longo ML. Role of unsaturated lipid and ergosterol in ethanol tolerance of model yeast biomembranes. Biophys J. 2012;102:507\u201316.","journal-title":"Biophys J"},{"key":"2663_CR38","doi-asserted-by":"crossref","unstructured":"Kato S, Yoshida M, Izawa S. Btn2 is involved in the clearance of denatured proteins caused by severe ethanol stress in Saccharomyces cerevisiae. FEMS Yeast Res. 2019;19.","DOI":"10.1093\/femsyr\/foz079"},{"key":"2663_CR39","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature10317","volume":"475","author":"FU Hartl","year":"2011","unstructured":"Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature. 2011;475:324\u201332.","journal-title":"Nature"},{"key":"2663_CR40","doi-asserted-by":"crossref","unstructured":"Orlandi I, Ronzulli R, Casatta N, Vai M. Ethanol and acetate acting as carbon\/energy sources negatively affect yeast chronological aging. Oxid Med Cell Longev. 2013;2013:802870.","DOI":"10.1155\/2013\/802870"},{"key":"2663_CR41","doi-asserted-by":"crossref","unstructured":"Blomberg A. Yeast osmoregulation - glycerol still in pole position. FEMS Yeast Res. 2022;22.","DOI":"10.1093\/femsyr\/foac035"}],"container-title":["Microbial Cell Factories"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-025-02663-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12934-025-02663-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-025-02663-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T05:40:52Z","timestamp":1738215652000},"score":1,"resource":{"primary":{"URL":"https:\/\/microbialcellfactories.biomedcentral.com\/articles\/10.1186\/s12934-025-02663-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2663"],"URL":"https:\/\/doi.org\/10.1186\/s12934-025-02663-7","relation":{},"ISSN":["1475-2859"],"issn-type":[{"value":"1475-2859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]},"assertion":[{"value":"25 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33"}}