{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:16:42Z","timestamp":1790345802697,"version":"4.1.0"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-150535OB-I00"],"award-info":[{"award-number":["PID2023-150535OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-150535OB-I00"],"award-info":[{"award-number":["PID2023-150535OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-150535OB-I00"],"award-info":[{"award-number":["PID2023-150535OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-150535OB-I00"],"award-info":[{"award-number":["PID2023-150535OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-150535OB-I00"],"award-info":[{"award-number":["PID2023-150535OB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2023 PROD 00006"],"award-info":[{"award-number":["2023 PROD 00006"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2023 PROD 00006"],"award-info":[{"award-number":["2023 PROD 00006"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2023 PROD 00006"],"award-info":[{"award-number":["2023 PROD 00006"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-20192-6","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:57:05Z","timestamp":1760453825000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Signaling pathways contributing to the transcriptional response to alkalinization in Komagataella phaffii: role of the transcription factors Crz1 and Rim101"],"prefix":"10.1038","volume":"15","author":[{"given":"Marcel","family":"Albacar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Casamayor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelghani","family":"Zekhnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asier","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Ari\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"20192_CR1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.copbio.2017.12.010","volume":"53","author":"KR Love","year":"2018","unstructured":"Love, K. R., Dalvie, N. C. & Love, J. C. The yeast stands alone: the future of protein biologic production. Curr Opin Biotechnol 53, 50\u201358 (2018).","journal-title":"Curr Opin Biotechnol"},{"key":"20192_CR2","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/biom13030441","volume":"13","author":"GD Barone","year":"2023","unstructured":"Barone, G. D. et al. Industrial production of proteins with Pichia pastoris: Komagataella phaffii. Biomolecules 13, 441 (2023).","journal-title":"Biomolecules"},{"issue":"7","key":"20192_CR3","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1007\/s12033-023-00803-1","volume":"66","author":"VE Vijayakumar","year":"2023","unstructured":"Vijayakumar, V. E. & Venkataraman, K. A systematic review of the potential of Pichia pastoris (Komagataella phaffii) as an alternative host for biologics production. Mol. Biotechnol.\u00a066(7), 1821\u20131639 (2023).","journal-title":"Mol. Biotechnol."},{"key":"20192_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.engmic.2023.100094","volume":"3","author":"X Wu","year":"2023","unstructured":"Wu, X., Cai, P., Yao, L. & Zhou, Y. J. Genetic tools for metabolic engineering of Pichia pastoris. Eng Microbiol 3, 100094 (2023).","journal-title":"Eng Microbiol"},{"issue":"1","key":"20192_CR5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/1475-2859-11-103","volume":"11","author":"AL Vanz","year":"2012","unstructured":"Vanz, A. L. et al. Physiological response of Pichia pastoris GS115 to methanol-induced high level production of the Hepatitis B surface antigen: Catabolic adaptation, stress responses, and autophagic processes. Microb Cell Fact 11(1), 103 (2012).","journal-title":"Microb Cell Fact"},{"key":"20192_CR6","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s00253-021-11100-9","volume":"105","author":"L Jia","year":"2021","unstructured":"Jia, L. et al. Enhanced human lysozyme production by Pichia pastoris via periodic glycerol and dissolved oxygen concentrations control. Appl Microbiol Biotechnol 105, 1041\u20131050 (2021).","journal-title":"Appl Microbiol Biotechnol"},{"key":"20192_CR7","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/bit.260110302","volume":"11","author":"CL Cooney","year":"1969","unstructured":"Cooney, C. L., Wang, D. I. C. & Mateles, R. I. Measurement of heat evolution and correlation with oxygen consumption during microbial growth. Biotechnol Bioeng 11, 269\u2013281 (1969).","journal-title":"Biotechnol Bioeng"},{"key":"20192_CR8","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1002\/bit.27303","volume":"117","author":"D Zavec","year":"2020","unstructured":"Zavec, D., Gasser, B. & Mattanovich, D. Characterization of methanol utilization negative Pichia pastoris for secreted protein production: New cultivation strategies for current and future applications. Biotechnol Bioeng 117, 1394\u20131405 (2020).","journal-title":"Biotechnol Bioeng"},{"key":"20192_CR9","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jbiotec.2010.09.957","volume":"150","author":"G Stadlmayr","year":"2010","unstructured":"Stadlmayr, G. et al. Identification and characterisation of novel Pichia pastoris promoters for heterologous protein production. J Biotechnol 150, 519\u2013529 (2010).","journal-title":"J Biotechnol"},{"key":"20192_CR10","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1002\/bit.26800","volume":"115","author":"R Prielhofer","year":"2018","unstructured":"Prielhofer, R. et al. Superior protein titers in half the fermentation time: Promoter and process engineering for the glucose-regulated GTH1 promoter of Pichia pastoris. Biotechnol Bioeng 115, 2479\u20132488 (2018).","journal-title":"Biotechnol Bioeng"},{"key":"20192_CR11","doi-asserted-by":"publisher","first-page":"11358","DOI":"10.1093\/nar\/gkad752","volume":"51","author":"M Flores-Villegas","year":"2023","unstructured":"Flores-Villegas, M. et al. Systematic sequence engineering enhances the induction strength of the glucose-regulated GTH1 promoter of Komagataella phaffii. Nucleic Acids Res 51, 11358\u201311374 (2023).","journal-title":"Nucleic Acids Res"},{"key":"20192_CR12","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1002\/bit.26529","volume":"115","author":"T Vogl","year":"2018","unstructured":"Vogl, T. et al. Methanol independent induction in Pichia pastoris by simple derepressed overexpression of single transcription factors. Biotechnol Bioeng 115, 1037\u20131050 (2018).","journal-title":"Biotechnol Bioeng"},{"key":"20192_CR13","doi-asserted-by":"publisher","first-page":"41850","DOI":"10.1038\/srep41850","volume":"7","author":"J Wang","year":"2017","unstructured":"Wang, J. et al. Methanol-independent protein expression by AOX1 Promoter with trans-acting elements engineering and glucose-glycerol-shift induction in Pichia pastoris. Sci Rep 7, 41850 (2017).","journal-title":"Sci Rep"},{"key":"20192_CR14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13568-020-00972-1","volume":"10","author":"T Vogl","year":"2020","unstructured":"Vogl, T. et al. Orthologous promoters from related methylotrophic yeasts surpass expression of endogenous promoters of Pichia pastoris. AMB Express 10, 38 (2020).","journal-title":"AMB Express"},{"key":"20192_CR15","doi-asserted-by":"publisher","first-page":"249","DOI":"10.5941\/MYCO.2011.39.4.249","volume":"39","author":"K Selvig","year":"2011","unstructured":"Selvig, K. & Alspaugh, J. A. pH Response pathways in fungi: Adapting to host-derived and environmental signals. Mycobiology 39, 249\u2013256 (2011).","journal-title":"Mycobiology"},{"key":"20192_CR16","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1089\/omi.2010.0044","volume":"14","author":"J Ari\u00f1o","year":"2010","unstructured":"Ari\u00f1o, J. Integrative responses to high pH stress in S. cerevisiae. OMICS 14, 517\u2013523 (2010).","journal-title":"OMICS"},{"key":"20192_CR17","doi-asserted-by":"publisher","first-page":"182","DOI":"10.15698\/mic2015.06.205","volume":"2","author":"A Serra-Cardona","year":"2015","unstructured":"Serra-Cardona, A., Canadell, D. & Ari\u00f1o, J. Coordinate responses to alkaline pH stress in budding yeast. Microbial Cell 2, 182\u2013196 (2015).","journal-title":"Microbial Cell"},{"key":"20192_CR18","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1111\/j.1742-4658.2012.08548.x","volume":"279","author":"T Maeda","year":"2012","unstructured":"Maeda, T. The signaling mechanism of ambient pH sensing and adaptation in yeast and fungi. FEBS. J. 279, 1407\u20131413 (2012).","journal-title":"FEBS. J."},{"key":"20192_CR19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1128\/EC.00313-13","volume":"13","author":"M Cornet","year":"2014","unstructured":"Cornet, M. & Gaillardin, C. pH signaling in human fungal pathogens: a new target for antifungal strategies. Eukaryot Cell 13, 342\u2013352 (2014).","journal-title":"Eukaryot Cell"},{"key":"20192_CR20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12934-023-02074-6","volume":"22","author":"M Albacar","year":"2023","unstructured":"Albacar, M. et al. Transcriptomic profiling of the yeast Komagataella phaffii in response to environmental alkalinization. Microb Cell Fact 22, 63 (2023).","journal-title":"Microb Cell Fact"},{"key":"20192_CR21","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12934-024-02362-9","volume":"23","author":"M Albacar","year":"2024","unstructured":"Albacar, M., Casamayor, A. & Ari\u00f1o, J. Harnessing alkaline-pH regulatable promoters for efficient methanol-free expression of enzymes of industrial interest in Komagataella phaffii. Microb. Cell. Factories 23, 99 (2024).","journal-title":"Microb. Cell. Factories"},{"key":"20192_CR22","first-page":"1","volume":"12","author":"A Roy","year":"2020","unstructured":"Roy, A., Kumar, A., Baruah, D. & Tamuli, R. Calcium signaling is involved in diverse cellular processes in fungi. Mycology 12, 1\u201315 (2020).","journal-title":"Mycology"},{"key":"20192_CR23","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.tim.2008.03.006","volume":"16","author":"MA Penalva","year":"2008","unstructured":"Penalva, M. A., Tilburn, J., Bignell, E. & Arst, H. N. Jr. Ambient pH gene regulation in fungi: Making connections. Trends Microbiol. 16, 291\u2013300 (2008).","journal-title":"Trends Microbiol."},{"key":"20192_CR24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1093\/genetics\/145.1.63","volume":"145","author":"W Li","year":"1997","unstructured":"Li, W. & Mitchell, A. P. Proteolytic activation of Rim1p, a positive regulator of yeast sporulation and invasive growth. Genetics 145, 63\u201373 (1997).","journal-title":"Genetics"},{"key":"20192_CR25","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1128\/MCB.23.2.677-686.2003","volume":"23","author":"TM Lamb","year":"2003","unstructured":"Lamb, T. M. & Mitchell, A. P. The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol. Cell. Biol. 23, 677\u2013686 (2003).","journal-title":"Mol. Cell. Biol."},{"key":"20192_CR26","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.bbrc.2013.09.015","volume":"439","author":"SB Lee","year":"2013","unstructured":"Lee, S. B., Kang, H. S. & Kim, T. S. Nrg1 functions as a global transcriptional repressor of glucose-repressed genes through its direct binding to the specific promoter regions. Biochem Biophys Res Commun 439, 501\u2013505 (2013).","journal-title":"Biochem Biophys Res Commun"},{"key":"20192_CR27","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1111\/j.1365-2958.2004.04350.x","volume":"54","author":"ES Bensen","year":"2004","unstructured":"Bensen, E. S., Martin, S. J., Li, M., Berman, J. & Davis, D. A. Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. Mol. Microbiol. 54, 1335\u20131351 (2004).","journal-title":"Mol. Microbiol."},{"key":"20192_CR28","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1128\/EC.00038-14","volume":"13","author":"S Thewes","year":"2014","unstructured":"Thewes, S. Calcineurin-Crz1 signaling in lower eukaryotes. Eukaryot. Cell 13, 694\u2013705 (2014).","journal-title":"Eukaryot. Cell"},{"key":"20192_CR29","doi-asserted-by":"publisher","first-page":"43614","DOI":"10.1074\/jbc.M403606200","volume":"279","author":"L Viladevall","year":"2004","unstructured":"Viladevall, L. et al. Characterization of the calcium-mediated response to alkaline stress in Saccharomyces cerevisiae. J. Biol. Chem. 279, 43614\u201343624 (2004).","journal-title":"J. Biol. Chem."},{"key":"20192_CR30","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/j.1567-1364.2011.00730.x","volume":"11","author":"H Wang","year":"2011","unstructured":"Wang, H. et al. Alkaline stress triggers an immediate calcium fluctuation in Candida albicans mediated by Rim101p and Crz1p transcription factors. FEMS Yeast Res. 11, 430\u2013439 (2011).","journal-title":"FEMS Yeast Res."},{"key":"20192_CR31","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1186\/s12864-016-3006-6","volume":"17","author":"A Roque","year":"2016","unstructured":"Roque, A., Petrezs\u00e9lyov\u00e1, S., Serra-Cardona, A. & Ari\u00f1o, J. Genome-wide recruitment profiling of transcription factor Crz1 in response to high pH stress. BMC Genom 17, 662 (2016).","journal-title":"BMC Genom"},{"key":"20192_CR32","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1042\/BJ20080344","volume":"414","author":"A Spielvogel","year":"2008","unstructured":"Spielvogel, A. et al. Two zinc finger transcription factors, CrzA and SltA, are involved in cation homoeostasis and detoxification in Aspergillus nidulans. Biochem J 414, 419\u2013429 (2008).","journal-title":"Biochem J"},{"key":"20192_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12964-019-0473-9","volume":"18","author":"H Xu","year":"2020","unstructured":"Xu, H., Fang, T., Omran, R. P., Whiteway, M. & Jiang, L. RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans. Cell Commun Signaling 18, 1 (2020).","journal-title":"Cell Commun Signaling"},{"key":"20192_CR34","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1111\/j.1365-2958.2005.05037.x","volume":"59","author":"M Karababa","year":"2006","unstructured":"Karababa, M. et al. CRZ1, a target of the calcineurin pathway in Candida albicans. Mol Microbiol 59, 1429\u20131451 (2006).","journal-title":"Mol Microbiol"},{"key":"20192_CR35","doi-asserted-by":"publisher","first-page":"31079","DOI":"10.1074\/jbc.M202718200","volume":"277","author":"H Yoshimoto","year":"2002","unstructured":"Yoshimoto, H. et al. Genome-wide analysis of gene expression regulated by the calcineurin\/Crz1p signaling pathway in Saccharomyces cerevisiae. J. Biol. Chem. 277, 31079\u201331088 (2002).","journal-title":"J. Biol. Chem."},{"key":"20192_CR36","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.molcel.2007.02.014","volume":"25","author":"J Roy","year":"2007","unstructured":"Roy, J., Li, H., Hogan, P. G. & Cyert, M. S. A conserved docking site modulates substrate affinity for calcineurin, signaling output, and in vivo function. Mol Cell 25, 889\u2013901 (2007).","journal-title":"Mol Cell"},{"key":"20192_CR37","doi-asserted-by":"publisher","first-page":"D344","DOI":"10.1093\/nar\/gks1067","volume":"41","author":"CJA Sigrist","year":"2013","unstructured":"Sigrist, C. J. A. et al. New and continuing developments at PROSITE. Nucleic Acids Res 41, D344\u2013D347 (2013).","journal-title":"Nucleic Acids Res"},{"key":"20192_CR38","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/microorganisms13010039","volume":"13","author":"VV Ishtuganova","year":"2024","unstructured":"Ishtuganova, V. V., Sidorin, A. V., Makeeva, A. S., Padkina, M. V. & Rumyantsev, A. M. Effect of phosphate starvation on gene expression in Komagataella phaffii cells. Microorganisms 13, 39 (2024).","journal-title":"Microorganisms"},{"key":"20192_CR39","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1093\/bioinformatics\/bth078","volume":"20","author":"MJ de Hoon","year":"2004","unstructured":"de Hoon, M. J., Imoto, S., Nolan, J. & Miyano, S. Open source clustering software. Bioinformatics 20, 1453\u20131454 (2004).","journal-title":"Bioinformatics"},{"key":"20192_CR40","doi-asserted-by":"publisher","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","volume":"20","author":"AJ Saldanha","year":"2004","unstructured":"Saldanha, A. J. Java Treeview\u2013extensible visualization of microarray data. Bioinformatics 20, 3246\u20133248 (2004).","journal-title":"Bioinformatics"},{"key":"20192_CR41","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/mmi.12294","volume":"89","author":"P Hern\u00e1ndez-Ortiz","year":"2013","unstructured":"Hern\u00e1ndez-Ortiz, P. & Espeso, E. A. Phospho-regulation and nucleocytoplasmic trafficking of CrzA in response to calcium and alkaline-pH stress in Aspergillus nidulans. Mol Microbiol 89, 532\u2013551 (2013).","journal-title":"Mol Microbiol"},{"key":"20192_CR42","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1074\/jbc.M008381200","volume":"276","author":"TM Lamb","year":"2001","unstructured":"Lamb, T. M., Xu, W., Diamond, A. & Mitchell, A. P. Alkaline response genes of Saccharomyces cerevisiae and their relationship to the RIM101 pathway. J. Biol. Chem. 276, 1850\u20131856 (2001).","journal-title":"J. Biol. Chem."},{"key":"20192_CR43","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1111\/j.1365-2958.2007.05929.x","volume":"66","author":"AL Kullas","year":"2007","unstructured":"Kullas, A. L., Martin, S. J. & Davis, D. Adaptation to environmental pH: Integrating the Rim101 and calcineurin signal transduction pathways. Mol. Microbiol. 66, 858\u2013871 (2007).","journal-title":"Mol. Microbiol."},{"key":"20192_CR44","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1046\/j.1365-2958.2002.03246.x","volume":"46","author":"R Serrano","year":"2002","unstructured":"Serrano, R., Ruiz, A., Bernal, D., Chambers, J. R. & Arino, J. The transcriptional response to alkaline pH in Saccharomyces cerevisiae: evidence for calcium-mediated signalling. Mol. Microbiol. 46, 1319\u20131333 (2002).","journal-title":"Mol. Microbiol."},{"key":"20192_CR45","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1101\/gad.11.24.3445","volume":"11","author":"DP Matheos","year":"1997","unstructured":"Matheos, D. P., Kingsbury, T. J., Ahsan, U. S. & Cunningham, K. W. Tcn1p\/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. Genes Dev. 11, 3445\u20133458 (1997).","journal-title":"Genes Dev."},{"key":"20192_CR46","doi-asserted-by":"publisher","first-page":"3432","DOI":"10.1101\/gad.11.24.3432","volume":"11","author":"AM Stathopoulos","year":"1997","unstructured":"Stathopoulos, A. M. & Cyert, M. S. Calcineurin acts through the CRZ1\/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 11, 3432\u20133444 (1997).","journal-title":"Genes Dev."},{"key":"20192_CR47","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00294-005-0003-8","volume":"48","author":"M Santos","year":"2005","unstructured":"Santos, M. & de Larrinoa, I. F. Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor. Curr Genet 48, 88\u2013100 (2005).","journal-title":"Curr Genet"},{"key":"20192_CR48","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00294-008-0220-z","volume":"54","author":"D Hagiwara","year":"2008","unstructured":"Hagiwara, D., Kondo, A., Fujioka, T. & Abe, K. Functional analysis of C2H2 zinc finger transcription factor CrzA involved in calcium signaling in Aspergillus nidulans. Curr Genet 54, 325\u2013338 (2008).","journal-title":"Curr Genet"},{"key":"20192_CR49","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1111\/mmi.14234","volume":"111","author":"D Gohain","year":"2019","unstructured":"Gohain, D. & Tamuli, R. Calcineurin responsive zinc-finger-1 binds to a unique promoter sequence to upregulate neuronal calcium sensor-1, whose interaction with MID-1 increases tolerance to calcium stress in Neurospora crassa. Mol Microbiol 111, 1510\u20131528 (2019).","journal-title":"Mol Microbiol"},{"key":"20192_CR50","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1128\/EC.2.5.937-948.2003","volume":"2","author":"A Ruiz","year":"2003","unstructured":"Ruiz, A., Yenush, L. & Ari\u00f1o, J. Regulation of ENA1 Na+-ATPase gene expression by the Ppz1 protein phosphatase is mediated by the calcineurin pathway. Eukaryot Cell 2, 937\u2013948 (2003).","journal-title":"Eukaryot Cell"},{"key":"20192_CR51","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1128\/EC.00194-08","volume":"7","author":"P Wei\u00df","year":"2008","unstructured":"Wei\u00df, P., Huppert, S. & K\u00f6lling, R. ESCRT-III protein Snf7 mediates high-level expression of the SUC2 gene via the Rim101 pathway. Eukaryot Cell 7, 1888\u20131894 (2008).","journal-title":"Eukaryot Cell"},{"key":"20192_CR52","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s004380050929","volume":"260","author":"E Futai","year":"1999","unstructured":"Futai, E. et al. The protease activity of a calpain-like cysteine protease in Saccharomyces cerevisiae is required for alkaline adaptation and sporulation. Mol Gen Genet 260, 559\u2013568 (1999).","journal-title":"Mol Gen Genet"},{"key":"20192_CR53","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1128\/EC.5.3.507-517.2006","volume":"5","author":"F Castrejon","year":"2006","unstructured":"Castrejon, F., Gomez, A., Sanz, M., Duran, A. & Roncero, C. The RIM101 pathway contributes to yeast cell wall assembly and its function becomes essential in the absence of mitogen-activated protein kinase Slt2p. Eukaryot. Cell 5, 507\u2013517 (2006).","journal-title":"Eukaryot. Cell"},{"key":"20192_CR54","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1128\/EC.3.6.1609-1618.2004","volume":"3","author":"AL Kullas","year":"2004","unstructured":"Kullas, A. L., Li, M. & Davis, D. A. Snf7p, a component of the ESCRT-III protein complex, is an upstream member of the RIM101 pathway in Candida albicans. Eukaryot Cell 3, 1609\u20131618 (2004).","journal-title":"Eukaryot Cell"},{"key":"20192_CR55","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1093\/genetics\/162.4.1573","volume":"162","author":"DA Davis","year":"2002","unstructured":"Davis, D. A., Bruno, V. M., Loza, L., Filler, S. G. & Mitchell, A. P. Candida albicans Mds3p, a conserved regulator of pH responses and virulence identified through insertional mutagenesis. Genetics 162, 1573\u20131581 (2002).","journal-title":"Genetics"},{"key":"20192_CR56","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1128\/AAC.00391-06","volume":"50","author":"M Cornet","year":"2006","unstructured":"Cornet, M., Gaillardin, C. & Richard, M. L. Deletions of the endocytic components VPS28 and VPS32 in Candida albicans lead to echinocandin and azole hypersensitivity. Antimicrob Agents Chemother 50, 3492\u20133495 (2006).","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"20192_CR57","doi-asserted-by":"publisher","first-page":"e1000776","DOI":"10.1371\/journal.ppat.1000776","volume":"6","author":"TR O\u2019Meara","year":"2010","unstructured":"O\u2019Meara, T. R. et al. Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog 6(2), e1000776 (2010).","journal-title":"PLoS Pathog"},{"key":"20192_CR58","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.ygeno.2012.09.005","volume":"101","author":"Y Zhao","year":"2013","unstructured":"Zhao, Y., Du, J., Zhao, G. & Jiang, L. Activation of calcineurin is mainly responsible for the calcium sensitivity of gene deletion mutations in the genome of budding yeast. Genomics 101, 49\u201356 (2013).","journal-title":"Genomics"},{"key":"20192_CR59","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.bbrc.2020.03.163","volume":"527","author":"F Zhao","year":"2020","unstructured":"Zhao, F. et al. Multiple cellular responses guarantee yeast survival in presence of the cell membrane\/wall interfering agent sodium dodecyl sulfate. Biochem Biophys Res Commun 527, 276\u2013282 (2020).","journal-title":"Biochem Biophys Res Commun"},{"key":"20192_CR60","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12866-020-1721-2","volume":"20","author":"C Cao","year":"2020","unstructured":"Cao, C., Cao, Z., Yu, P. & Zhao, Y. Genome-wide identification for genes involved in sodium dodecyl sulfate toxicity in Saccharomyces cerevisiae. BMC Microbiol 20, 34 (2020).","journal-title":"BMC Microbiol"},{"key":"20192_CR61","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01689-23","volume":"12","author":"L Jiang","year":"2024","unstructured":"Jiang, L. et al. Transcriptional expression of PHR2 is positively controlled by the calcium signaling transcription factor Crz1 through its binding motif in the promoter. Microbiol Spectr 12, e0168923 (2024).","journal-title":"Microbiol Spectr"},{"key":"20192_CR62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158424","volume":"11","author":"S Petrezs\u00e9lyov\u00e1","year":"2016","unstructured":"Petrezs\u00e9lyov\u00e1, S. et al. Regulation of the Na+\/K+-ATPase Ena1 expression by calcineurin\/Crz1 under high pH stress: A quantitative study. PLoS ONE 11, e0158424 (2016).","journal-title":"PLoS ONE"},{"key":"20192_CR63","doi-asserted-by":"publisher","first-page":"13923","DOI":"10.1074\/jbc.M708683200","volume":"283","author":"A Ruiz","year":"2008","unstructured":"Ruiz, A., Serrano, R. & Arino, J. Direct regulation of genes involved in glucose utilization by the calcium\/calcineurin pathway. J. Biol. Chem. 283, 13923\u201313933 (2008).","journal-title":"J. Biol. Chem."},{"key":"20192_CR64","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1083\/jcb.124.3.351","volume":"124","author":"KW Cunningham","year":"1994","unstructured":"Cunningham, K. W. & Fink, G. R. Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. J. Cell Biol. 124, 351\u2013363 (1994).","journal-title":"J. Cell Biol."},{"key":"20192_CR65","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1046\/j.1365-2958.2003.03495.x","volume":"48","author":"D Sanglard","year":"2003","unstructured":"Sanglard, D., Ischer, F., Marchetti, O., Entenza, J. & Bille, J. Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Mol. Microbiol. 48, 959\u2013976 (2003).","journal-title":"Mol. Microbiol."},{"key":"20192_CR66","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1128\/EC.00337-07","volume":"6","author":"A Ruiz","year":"2007","unstructured":"Ruiz, A. & Ari\u00f1o, J. Function and regulation of the Saccharomyces cerevisiae ENA sodium ATPase system. Eukaryot Cell 6, 2175\u20132183 (2007).","journal-title":"Eukaryot Cell"},{"key":"20192_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1574-6968.2011.02214.x","volume":"317","author":"J Ramos","year":"2011","unstructured":"Ramos, J., Ari\u00f1o, J. & Sychrov\u00e1, H. Alkali-metal-cation influx and efflux systems in nonconventional yeast species. FEMS Microbiol Lett 317, 1\u20138 (2011).","journal-title":"FEMS Microbiol Lett"},{"key":"20192_CR68","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0014-5793(96)00157-3","volume":"382","author":"JA M\u00e1rquez","year":"1996","unstructured":"M\u00e1rquez, J. A. & Serrano, R. Multiple transduction pathways regulate the sodium-extrusion gene PMR2\/ENA1 during salt stress in yeast. FEBS Lett 382, 89\u201392 (1996).","journal-title":"FEBS Lett"},{"key":"20192_CR69","doi-asserted-by":"publisher","first-page":"36632","DOI":"10.1074\/jbc.M606483200","volume":"281","author":"M Platara","year":"2006","unstructured":"Platara, M. et al. The transcriptional response of the yeast Na+-ATPase ENA1 Gene to alkaline stress involves three main signaling pathways. J. Biol. Chem. 281, 36632\u201336642 (2006).","journal-title":"J. Biol. Chem."},{"key":"20192_CR70","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1042\/BJ20112099","volume":"444","author":"A Casamayor","year":"2012","unstructured":"Casamayor, A. et al. The role of the Snf1 kinase in the adaptive response of Saccharomyces cerevisiae to alkaline pH stress. Biochem J 444, 39\u201349 (2012).","journal-title":"Biochem J"},{"key":"20192_CR71","doi-asserted-by":"publisher","first-page":"14325","DOI":"10.1038\/s41598-020-71297-z","volume":"10","author":"A Markina-I\u00f1arrairaegui","year":"2020","unstructured":"Markina-I\u00f1arrairaegui, A., Spielvogel, A., Etxebeste, O., Ugalde, U. & Espeso, E. A. Tolerance to alkaline ambient pH in Aspergillus nidulans depends on the activity of ENA proteins. Sci Rep 10, 14325 (2020).","journal-title":"Sci Rep"},{"key":"20192_CR72","first-page":"1","volume":"6","author":"I Picazo","year":"2020","unstructured":"Picazo, I., Etxebeste, O., Requena, E., Garzia, A. & Espeso, E. A. Defining the transcriptional responses of Aspergillus nidulans to cation\/alkaline pH stress and the role of the transcription factor SltA. Microb Genom 6, 1\u201318 (2020).","journal-title":"Microb Genom"},{"key":"20192_CR73","doi-asserted-by":"publisher","first-page":"4881","DOI":"10.1007\/s00253-019-09858-0","volume":"103","author":"A Tominaga","year":"2019","unstructured":"Tominaga, A. et al. Catechol O-methyltransferase homologs in Schizosaccharomyces pombe are response factors to alkaline and salt stress. Appl Microbiol Biotechnol 103, 4881\u20134887 (2019).","journal-title":"Appl Microbiol Biotechnol"},{"key":"20192_CR74","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1111\/j.1567-1364.2008.00408.x","volume":"8","author":"RA Zvyagilskaya","year":"2008","unstructured":"Zvyagilskaya, R. A. et al. Characterization of the Pho89 phosphate transporter by functional hyperexpression in Saccharomyces cerevisiae. FEMS Yeast Res. 8, 685\u2013696 (2008).","journal-title":"FEMS Yeast Res."},{"key":"20192_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011156","volume":"20","author":"M Acosta-Zald\u00edvar","year":"2024","unstructured":"Acosta-Zald\u00edvar, M. et al. Candida albicans\u2019 inorganic phosphate transport and evolutionary adaptation to phosphate scarcity. PLoS Genet 20, e1011156 (2024).","journal-title":"PLoS Genet"},{"key":"20192_CR76","doi-asserted-by":"publisher","first-page":"3528","DOI":"10.1128\/AEM.02913-08","volume":"75","author":"J Ahn","year":"2009","unstructured":"Ahn, J. et al. Phosphate-responsive promoter of a Pichia pastoris sodium phosphate symporter. Appl Environ Microbiol 75, 3528\u20133534 (2009).","journal-title":"Appl Environ Microbiol"},{"key":"20192_CR77","doi-asserted-by":"publisher","first-page":"4420","DOI":"10.1128\/MCB.01089-14","volume":"34","author":"A Serra-Cardona","year":"2014","unstructured":"Serra-Cardona, A., Petrezs\u00e9lyov\u00e1, S., Canadell, D., Ramos, J. & Ari\u00f1o, J. Coregulated expression of the Na+\/phosphate Pho89 transporter and Ena1 Na+-ATPase allows their functional coupling under high-pH stress. Mol Cell Biol 34, 4420\u20134435 (2014).","journal-title":"Mol Cell Biol"},{"key":"20192_CR78","doi-asserted-by":"publisher","first-page":"e70213","DOI":"10.1111\/1751-7915.70213","volume":"18","author":"A Zekhnini","year":"2025","unstructured":"Zekhnini, A., Casamayor, A. & Ari\u00f1o, J. Combinatorial alkali-responsive hybrid promoters as tools for heterologous protein expression in Saccharomyces cerevisiae. Microb. Biotechnol. 18, e70213. https:\/\/doi.org\/10.1111\/1751-7915.70213 (2025),","journal-title":"Microb. Biotechnol."},{"key":"20192_CR79","volume-title":"Molecular cloning: a laboratory manual","author":"MR Green","year":"2012","unstructured":"Green, M. R. & Sambrook, J. Molecular cloning: a laboratory manual (Cold Spring Harbor Laboratory Press, 2012)."},{"key":"20192_CR80","doi-asserted-by":"publisher","first-page":"44","DOI":"10.2144\/05381BM04","volume":"38","author":"J Lin-Cereghino","year":"2005","unstructured":"Lin-Cereghino, J. et al. Condensed protocol for competent cell preparation and transformation of the methylotrophic yeast Pichia pastoris. Biotechniques 38, 44\u201348 (2005).","journal-title":"Biotechniques"},{"key":"20192_CR81","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/978-1-4939-9024-5_9","volume":"1923","author":"T Gassler","year":"2019","unstructured":"Gassler, T., Heistinger, L., Mattanovich, D., Gasser, B. & Prielhofer, R. CRISPR\/Cas9-mediated homology-directed genome editing in Pichia pastoris. Methods Mol Biol 1923, 211\u2013225 (2019).","journal-title":"Methods Mol Biol"},{"key":"20192_CR82","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12918-017-0492-3","volume":"11","author":"R Prielhofer","year":"2017","unstructured":"Prielhofer, R. et al. GoldenPiCS: A golden gate-derived modular cloning system for applied synthetic biology in the yeast Pichia pastoris. BMC Syst Biol 11, 123 (2017).","journal-title":"BMC Syst Biol"},{"key":"20192_CR83","doi-asserted-by":"publisher","first-page":"W171","DOI":"10.1093\/nar\/gkz365","volume":"47","author":"K Labun","year":"2019","unstructured":"Labun, K. et al. CHOPCHOP v3: Expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res 47, W171\u2013W174 (2019).","journal-title":"Nucleic Acids Res"},{"key":"20192_CR84","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods. 9, 357\u2013359 (2012).","journal-title":"Nat. Methods."},{"key":"20192_CR85","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"20192_CR86","doi-asserted-by":"publisher","first-page":"fow051","DOI":"10.1093\/femsyr\/fow051","volume":"16","author":"M Valli","year":"2016","unstructured":"Valli, M. et al. Curation of the genome annotation of Pichia pastoris (Komagataella phaffii) CBS7435 from gene level to protein function. FEMS Yeast Res 16, fow051 (2016).","journal-title":"FEMS Yeast Res"},{"key":"20192_CR87","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/1471-2105-13-S16-S6","volume":"13","author":"T Clough","year":"2012","unstructured":"Clough, T., Thaminy, S., Ragg, S., Aebersold, R. & Vitek, O. Statistical protein quantification and significance analysis in label-free LC-MS experiments with complex designs. BMC Bioinform 13, S6 (2012).","journal-title":"BMC Bioinform"},{"key":"20192_CR88","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","volume":"53","author":"Y Perez-Riverol","year":"2025","unstructured":"Perez-Riverol, Y. et al. The PRIDE database at 20 years: 2025 update. Nucleic Acids Res 53, D543\u2013D553 (2025).","journal-title":"Nucleic Acids Res"},{"key":"20192_CR89","doi-asserted-by":"publisher","first-page":"W207","DOI":"10.1093\/nar\/gkad347","volume":"51","author":"L Kolberg","year":"2023","unstructured":"Kolberg, L. et al. g:Profiler-interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update). Nucleic Acids Res 51, W207\u2013W212 (2023).","journal-title":"Nucleic Acids Res"},{"key":"20192_CR90","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1038\/nprot.2008.97","volume":"3","author":"JV Turatsinze","year":"2008","unstructured":"Turatsinze, J. V., Thomas-Chollier, M., Defrance, M. & van Helden, J. Using RSAT to scan genome sequences for transcription factor binding sites and cis-regulatory modules. Nat Protoc 3, 1578\u20131588 (2008).","journal-title":"Nat Protoc"},{"key":"20192_CR91","doi-asserted-by":"publisher","first-page":"W39","DOI":"10.1093\/nar\/gkv416","volume":"43","author":"TL Bailey","year":"2015","unstructured":"Bailey, T. L., Johnson, J., Grant, C. E. & Noble, W. S. The MEME suite. Nucleic Acids Res 43, W39\u2013W49 (2015).","journal-title":"Nucleic Acids Res"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20192-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20192-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20192-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T03:25:17Z","timestamp":1760844317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20192-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["20192"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-20192-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"3 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35841"}}