{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:29:18Z","timestamp":1784734158303,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Scientific Fund, the Republic of Bulgaria","award":["KP-06-N67\/11"],"award-info":[{"award-number":["KP-06-N67\/11"]}]},{"name":"French Embassy","award":["KP-06-N67\/11"],"award-info":[{"award-number":["KP-06-N67\/11"]}]},{"name":"French Institute in Bulgaria","award":["KP-06-N67\/11"],"award-info":[{"award-number":["KP-06-N67\/11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>2,3-Butanediol (2,3-BD) is an alcohol highly demanded in the chemical, pharmaceutical, and food industries. Its microbial production, safe non-pathogenic producer strains, and suitable substrates have been avidly sought in recent years. The present study investigated 2,3-BD synthesis by the GRAS Bacillus licheniformis 24 using chicory inulin as a cheap and renewable substrate. The process appears to be pH-dependent. At pH 5.25, the synthesis of 2,3-BD was barely detectable due to the lack of inulin hydrolysis. At pH 6.25, 2,3-BD concentration reached 67.5 g\/L with rapid hydrolysis of the substrate but was accompanied by exopolysaccharide (EPS) synthesis. Since inulin conversion by bacteria is a complex process and begins with its hydrolysis, the question of the acting enzymes arose. Genome mining revealed that several glycoside hydrolase (GH) enzymes from different CAZy families are involved. Five genes encoding such enzymes in B. licheniformis 24 were amplified and sequenced: sacA, sacB, sacC, levB, and fruA. Real-time RT-PCR experiments showed that the process of inulin hydrolysis is regulated at the level of gene expression, as four genes were significantly overexpressed at pH 6.25. In contrast, the expression of levB remained at the same level at the different pH values at all-time points. It was concluded that the sacC and sacA\/fruA genes are crucial for inulin hydrolysis. They encode exoinulinase (EC 3.2.1.80) and sucrases (EC 3.2.1.26), respectively. The striking overexpression of sacB under these conditions led to increased synthesis of EPS; therefore, the simultaneous production of 2,3-BD and EPS cannot be avoided.<\/jats:p>","DOI":"10.3390\/ijms241814065","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:57:56Z","timestamp":1694685476000},"page":"14065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Influence of pH on Inulin Conversion to 2,3-Butanediol by Bacillus licheniformis 24: A Gene Expression Assay"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6123-2719","authenticated-orcid":false,"given":"Lidia","family":"Tsigoriyna","sequence":"first","affiliation":[{"name":"Institute of Chemical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-9530","authenticated-orcid":false,"given":"Alexander","family":"Arsov","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanoel","family":"Gergov","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-5799","authenticated-orcid":false,"given":"Penka","family":"Petrova","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-0894","authenticated-orcid":false,"given":"Kaloyan","family":"Petrov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"ref_1","unstructured":"(2023, June 06). The EU\u2019s Green Deal Industrial Plan. Available online: https:\/\/www.edelmanglobaladvisory.com\/insights\/european-green-deal-industrial-plan."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/bbb.2173","article-title":"Technological development of the bio-based 2,3-butanediol process","volume":"15","author":"Borschiver","year":"2021","journal-title":"Biofuels Bioprod. Biorefining"},{"key":"ref_3","unstructured":"(2023, August 04). 2,3-Butanediol Market. Available online: https:\/\/www.transparencymarketresearch.com\/2-3-butanediol-market.html."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Petrov, K., and Petrova, P. (2021). Current Advances in Microbial Production of Acetoin and 2,3-Butanediol by Bacillus spp.. Fermentation, 7.","DOI":"10.3390\/fermentation7040307"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Song, D., Cho, S.-Y., Vu, T.-T., Duong, H.-P.-Y., and Kim, E. (2021). Dehydration of 2,3-Butanediol to 1,3-Butadiene and Methyl Ethyl Ketone: Modeling, Numerical Analysis and Validation Using Pilot-Scale Reactor Data. Catalysts, 11.","DOI":"10.3390\/catal11080999"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107783","DOI":"10.1016\/j.biotechadv.2021.107783","article-title":"Prospects on bio-based 2,3-butanediol and acetoin production: Recent progress and advances","volume":"54","author":"Maina","year":"2022","journal-title":"Biotechnol. Adv."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Lee, D.Y., Lee, S.K., Kim, H.R., Chun, Y., Yoo, H.Y., Kwak, H.S., Park, C., Lee, J.H., and Kim, S.W. (2021). Development of 2,3-Butanediol Production Process from Klebsiella aerogenes ATCC 29007 Using Extracted Sugars of Chlorella pyrenoidosa and Biodiesel-Derived Crude Glycerol. Processes, 9.","DOI":"10.3390\/pr9030517"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00253-016-7849-1","article-title":"Screening of novel bacteria for the 2,3-butanediol production","volume":"101","author":"Kallbach","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"409","DOI":"10.4014\/jmb.1710.10038","article-title":"Isolation and evaluation of Bacillus strains for industrial production of 2,3-butanediol","volume":"28","author":"Song","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1039\/C6GC01023G","article-title":"Contracted but effective: Production of enantiopure 2,3-butanediol by thermophilic and GRAS Bacillus licheniformis","volume":"18","author":"Ge","year":"2016","journal-title":"Green Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jbiosc.2020.02.009","article-title":"New Bacillus spp. with potential for 2,3-butanediol production from biomass","volume":"130","author":"Petrova","year":"2020","journal-title":"J. Biosci. Bioeng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.biortech.2012.08.047","article-title":"Enhanced fed-batch fermentation of 2,3-butanediol by Paenibacillus polymyxa DSM 365","volume":"124","author":"Schieder","year":"2012","journal-title":"Bioresour. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00253-012-4331-6","article-title":"Medium optimization and proteome analysis of (R,R)-2,3-butanediol production by Paenibacillus polymyxa ATCC 12321","volume":"97","author":"Li","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tsigoriyna, L., Ganchev, D., Petrova, P., and Petrov, K. (2021). Highly Efficient 2,3-Butanediol Production by Bacillus licheniformis via Complex Optimization of Nutritional and Technological Parameters. Fermentation, 7.","DOI":"10.3390\/fermentation7030118"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.1007\/s00253-013-4981-z","article-title":"Enhanced 2,3-butanediol production in fed batch cultures of free and immobilized Bacillus licheniformis DSM 8785","volume":"97","author":"Jurchescu","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_16","first-page":"183","article-title":"Production of 2,3-butanediol from Fructose by Bacillus licheniformis 24","volume":"37","author":"Tsigoriyna","year":"2021","journal-title":"Acta Microbiol. Bulg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0960-8524(03)00063-4","article-title":"Effects of temperature, inoculum size and starch hydrolyzate concentration on butanediol production by Bacillus licheniformis","volume":"89","author":"Perego","year":"2003","journal-title":"Bioresour. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.biortech.2014.07.101","article-title":"Efficient production of 2,3-butanediol from corn stover hydrolysate by using a thermophilic Bacillus licheniformis strain","volume":"170","author":"Li","year":"2014","journal-title":"Bioresour. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.biortech.2015.03.077","article-title":"Direct conversion of chicory flour into L(+)-lactic acid by the highly effective inulinase producer Lactobacillus paracasei DSM 23505","volume":"186","author":"Petrova","year":"2015","journal-title":"Bioresour. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s10295-017-1932-1","article-title":"Enhancement of 2,3-butanediol production from Jerusalem artichoke tuber extract by a recombinant Bacillus sp. strain BRC1 with increased inulinase activity","volume":"44","author":"Park","year":"2017","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00253-008-1823-5","article-title":"Microbial production of 2,3-butanediol from Jerusalem artichoke tubers by Klebsiella pneumoniae","volume":"82","author":"Sun","year":"2009","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.1016\/j.biortech.2010.03.143","article-title":"Optimization of medium for one-step fermentation of inulin extract from Jerusalem artichoke tubers using Paenibacillus polymyxa ZJ-9 to produce R, R-2,3-butanediol","volume":"101","author":"Gao","year":"2010","journal-title":"Bioresour. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9624","DOI":"10.1021\/acssuschemeng.2c02994","article-title":"Modular Metabolic Engineering of Bacillus licheniformis for Efficient 2,3-Butanediol Production by Consolidated Bioprocessing of Jerusalem Artichoke Tubers","volume":"10","author":"Guo","year":"2022","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6458","DOI":"10.1128\/AEM.01802-14","article-title":"Efficient simultaneous saccharification and fermentation of inulin to 2,3-butanediol by thermophilic Bacillus licheniformis ATCC 14580","volume":"80","author":"Li","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00726-018-02690-2","article-title":"Low-resolution structure, oligomerization and its role on the enzymatic activity of a sucrose-6-phosphate hydrolase from Bacillus licheniformis","volume":"51","author":"Mera","year":"2019","journal-title":"Amino Acids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10242422.2016.1196486","article-title":"Structural and functional properties of inulinases: A review","volume":"34","author":"Holyavka","year":"2016","journal-title":"Biocatal. Biotransform."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1007\/s00253-018-8854-3","article-title":"Rational designed mutagenesis of levansucrase from Bacillus licheniformis 8-37-0-1 for product specificity study","volume":"102","author":"He","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Doan, C.T., Tran, T.N., Nguyen, T.T., Tran, T.P.H., Nguyen, V.B., Tran, T.D., Nguyen, A.D., and Wang, S.-L. (2021). Production of Sucrolytic Enzyme by Bacillus licheniformis by the Bioconversion of Pomelo Albedo as a Carbon Source. Polymers, 13.","DOI":"10.3390\/polym13121959"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1021\/acs.jpcb.1c02016","article-title":"Computational Design of Oligosaccharide-Producing Levansucrase from Bacillus licheniformis RN-01 to Increase Its Stability at High Temperature","volume":"125","author":"Klaewkla","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.procbio.2014.02.005","article-title":"Levan-type FOS production using a Bacillus licheniformis endolevanase","volume":"49","author":"Escalante","year":"2014","journal-title":"Process Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tsigoriyna, L., Arsov, A., Petrova, P., Gergov, E., and Petrov, K. (2023). Heterologous Expression of Inulinase Gene in Bacillus licheniformis 24 for 2,3-Butanediol Production from Inulin. Catalysts, 13.","DOI":"10.3390\/catal13050841"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Petrova, P., Arsov, A., Ivanov, I., Tsigoriyna, L., and Petrov, K. (2021). New Exopolysaccharides Produced by Bacillus licheniformis 24 Display Substrate-Dependent Content and Antioxidant Activity. Microorganisms, 9.","DOI":"10.3390\/microorganisms9102127"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1186\/gb-2004-5-10-r77","article-title":"Complete genome sequence of the industrial bacterium Bacillus licheniformis and comparisons with closely related Bacillus species","volume":"5","author":"Rey","year":"2004","journal-title":"Genome Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.procbio.2020.08.018","article-title":"Bioconversion of inulin to 2,3-butanediol by a newly isolated Klebsiella pneumoniae producing inulinase","volume":"98","author":"Dai","year":"2020","journal-title":"Proc. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12011-016-0796-y","article-title":"Comparative Effects of Inulin with Different Polymerization Degrees on Growth Performance, Blood Trace Minerals, and Erythrocyte Indices in Growing-Finishing Pigs","volume":"176","author":"Grela","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF00253648","article-title":"2,3-Butanediol production from Jerusalem artichoke, Helianthus Tuberosus, by Bacillus polymyxa ATCC 12321. Optimization of kL a profile","volume":"25","author":"Fages","year":"1986","journal-title":"Appl. Microb. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez-Lorenzo, L., Porras-Dom\u00ednguez, J.R., Raga-Carbajal, E., Olvera, C., Rodr\u00edguez-Alegr\u00eda, M.E., Carrillo-Nava, E., Costas, M., and Mungu\u00eda, A.L. (2015). Intrinsic Levanase Activity of Bacillus subtilis 168 Levansucrase (SacB). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143394"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1128\/aem.61.5.1953-1958.1995","article-title":"Purification and characterization of the Bacillus subtilis levanase produced in Escherichia coli","volume":"61","author":"Wanker","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Marciniak, B.C., Pabijaniak, M., de Jong, A., D\u0171hring, R., Seidel, G., Hillen, W., and Kuipers, O.P. (2012). High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-401"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-6968.2010.02085.x","article-title":"Exopolymeric Substances (EPS) from Bacillus subtilis: Polymers and Genes Encoding Their Synthesis","volume":"313","author":"Marvasi","year":"2010","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/0022-2836(90)90284-S","article-title":"Levanase Operon of Bacillus Subtilis Includes a Fructose-Specific Phosphotransferase System Regulating the Expression of the Operon","volume":"214","author":"Klier","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dom\u017ca\u0142-K\u0119dzia, M., Ostrowska, M., Lewi\u0144ska, A., and \u0141ukaszewicz, M. (2023). Recent Developments and Applications of Microbial Levan, A Versatile Polysaccharide-Based Biopolymer. Molecules, 28.","DOI":"10.3390\/molecules28145407"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/10242420600986811","article-title":"Glycosylation with activated sugars using glycosyltransferases and transglycosidases","volume":"24","author":"Seibel","year":"2006","journal-title":"Biocatal. Biotransform."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.biotechadv.2008.05.001","article-title":"Glycosyltransferase-catalyzed synthesis of bioactive oligosaccharides","volume":"26","author":"Weijers","year":"2008","journal-title":"Biotechnol. Adv."},{"key":"ref_45","first-page":"465","article-title":"Properties of levansucrase from Bacillus circulans","volume":"45","author":"Guereca","year":"1996","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.biotechadv.2016.05.002","article-title":"Review of Levan polysaccharide: From a century of past experiences to future prospects","volume":"34","author":"Combie","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1080\/10408398.2018.1506421","article-title":"Recent advances in Levansucrase and Inulosucrase: Evolution, characteristics, and application","volume":"59","author":"Xu","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijbiomac.2012.11.017","article-title":"High expression level of levansucrase from Bacillus licheniformis RN-01 and synthesis of levan nanoparticles","volume":"54","author":"Nakapong","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.procbio.2014.05.012","article-title":"A recombinant levansucrase from Bacillus licheniformis 8-37-0-1 catalyzes versatile transfructosylation reactions","volume":"49","author":"Lu","year":"2014","journal-title":"Process Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1007\/s12010-016-2264-8","article-title":"Optimization of levan production by cold-active Bacillus licheniformis ANT 179 and fructooligosaccharide synthesis by its levansucrase","volume":"181","author":"Xavier","year":"2017","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1099\/mic.0.27366-0","article-title":"Autogenous modulation of the Bacillus subtilis sacB-levB-yveA levansucrase operon by the levB transcript","volume":"150","author":"Daguer","year":"2004","journal-title":"Microbiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ijbiomac.2016.01.008","article-title":"Levanase from Bacillus subtilis hydrolyses \u03b2-2,6 fructosyl bonds in bacterial levans and in grass fructans","volume":"85","author":"Jensen","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1099\/00221287-147-12-3413","article-title":"YveB, Encoding Endolevanase LevB, Is Part of the SacB-YveB-YveA Levansucrase Tricistronic Operon in Bacillus subtilis","volume":"147","author":"Pereira","year":"2001","journal-title":"Microbiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1128\/MMBR.00024-06","article-title":"How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria","volume":"70","author":"Deutscher","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1128\/jb.172.7.3966-3973.1990","article-title":"The sacT gene regulating the sacPA operon in Bacillus subtilis shares strong homology with transcriptional antiterminators","volume":"172","author":"Debarbouille","year":"1990","journal-title":"J. Bacteriol."},{"key":"ref_56","first-page":"e00213-18","article-title":"Cross Talk among Transporters of the Phosphoenolpyruvate-Dependent Phosphotransferase System in Bacillus subtilis","volume":"200","author":"Altenbuchner","year":"2018","journal-title":"J. Bacteriol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:50:35Z","timestamp":1760129435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":57,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241814065"],"URL":"https:\/\/doi.org\/10.3390\/ijms241814065","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]}}}