{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:41:35Z","timestamp":1781775695949,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Project for Introducing Talents of Guangxi Minzu University","award":["2020KJQD21"],"award-info":[{"award-number":["2020KJQD21"]}]},{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Program","doi-asserted-by":"crossref","award":["AB23075147"],"award-info":[{"award-number":["AB23075147"]}],"id":[{"id":"10.13039\/501100017691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Caffeine contamination threatens ecosystems and human health, with conventional remediation methods facing limitations. This study identified Desarmillaria tabescens as a potent caffeine-degrading fungus, achieving efficient degradation under optimized conditions (malt extract medium, 900 mg\/L caffeine, 28 \u00b0C, pH 8). HPLC analysis revealed key intermediates such as theobromine and 3-methylxanthine, confirming a branched catabolic pathway involving N-demethylation and C8 oxidation. Transcriptomic profiling identified nine consistently upregulated cytochrome P450 genes as core catalytic components, with three adjacent to a polyketide biosynthetic gene cluster potentially supporting oxidative reactions. A three-phase \u201cStress-Degradation-Homeostasis\u201d regulatory model was proposed, coordinating detoxification, energy metabolism, and secondary metabolism. These findings advance understanding of fungal caffeine degradation mechanisms and provide valuable genetic resources for bioremediation and low-caffeine product development.<\/jats:p>","DOI":"10.3390\/microorganisms13122720","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:03:13Z","timestamp":1764687793000},"page":"2720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic Insights into Caffeine Degradation Pathways in Desarmillaria tabescens"],"prefix":"10.3390","volume":"13","author":[{"given":"Junrui","family":"Wang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"},{"name":"College of Life Science and Technology, Guangxi University, Nanning 530005, China"},{"name":"Nanning New Technology Entrepreneur Center, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"},{"name":"Microbiology Research Institute, Guangxi Academy of Agricultural Sciences, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Chang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiguo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danping","family":"Meng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2279-5740","authenticated-orcid":false,"given":"Mingguo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-6182","authenticated-orcid":false,"given":"Jinzi","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning 530008, China"},{"name":"Nanning New Technology Entrepreneur Center, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihong","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Guangxi University, Nanning 530005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/10408390500400009","article-title":"Coffee and Health: A Review of Recent Human Research","volume":"46","author":"Higdon","year":"2006","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41430-019-0430-0","article-title":"Caffeine and Caffeine Metabolites in Relation to Hypertension in U.S. Adults","volume":"74","author":"Ngueta","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12934-020-01333-0","article-title":"Isolation, characterization and application of theophylline-degrading Aspergillus fungi","volume":"19","author":"Zhou","year":"2020","journal-title":"Microb Cell Fact."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1007\/s00284-021-02644-0","article-title":"Microbial Degradation of Caffeine Using Himalayan Psychrotolerant Pseudomonas sp.GBPI_Hb5 (MCC 3295)","volume":"78","author":"Thathola","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e01965-19","DOI":"10.1128\/AEM.01965-19","article-title":"Bioassay for Determining the Concentrations of Caffeine and Individual Methylxanthines in Complex Samples","volume":"85","author":"Gutierrez","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/1751-7915.12262","article-title":"Genetic Characterization of Caffeine Degradation by Bacteria and Its Potential Applications","volume":"8","author":"Summers","year":"2015","journal-title":"Microb. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1021\/sb4000146","article-title":"Decaffeination and Measurement of Caffeine Content by Addicted Escherichia coli with a Refactored N-Demethylation Operon from Pseudomonas Putida CBB5","volume":"2","author":"Quandt","year":"2013","journal-title":"ACS Synth. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1099\/mic.0.043612-0","article-title":"Characterization of a Broad-Specificity Non-Haem Iron N-Demethylase from Pseudomonas Putida CBB5 Capable of Utilizing Several Purine Alkaloids as Sole Carbon and Nitrogen Source","volume":"157","author":"Summers","year":"2011","journal-title":"Microbiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1006\/bbrc.1998.9102","article-title":"A Novel Pathway for the Metabolism of Caffeine by a Mixed Culture Consortium","volume":"249","author":"Madyastha","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1016\/j.jmb.2019.08.004","article-title":"Structural and Mechanistic Insights into Caffeine Degradation by the Bacterial N-Demethylase Complex","volume":"431","author":"Kim","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.biortech.2004.06.019","article-title":"Comparative Culturing of Pleurotus Spp. on Coffee Pulp and Wheat Straw: Biomass Production and Substrate Biodegradation","volume":"96","author":"Salmones","year":"2005","journal-title":"Bioresour. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0141-0229(00)00186-1","article-title":"Biological Detoxification of Coffee Husk by Filamentous Fungi Using a Solid State Fermentation System","volume":"27","author":"Brand","year":"2000","journal-title":"Enzym. Microb. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1007\/s00253-019-09883-z","article-title":"Caffeine Metabolism during Cultivation of Oyster Mushroom (Pleurotus ostreatus) with Spent Coffee Grounds","volume":"103","author":"Bell","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/1750-3841.15015","article-title":"LC-MS\/MS-Based Metabolomic Analysis of Caffeine-Degrading Fungus Aspergillus sydowii during Tea Fermentation","volume":"85","author":"Zhou","year":"2020","journal-title":"J. Food Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1007\/s10529-006-9196-2","article-title":"Catabolic Pathways and Biotechnological Applications of Microbial Caffeine Degradation","volume":"28","author":"Dash","year":"2006","journal-title":"Biotechnol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Khan, M.F., Rama, M., and Murphy, C.D. (2025). Biodegradation of Fluorinated \u03b2-Triketone Herbicide Tembotrione by a Bacterial\u2013Fungal Consortium. Biocatal. Agric. Biotechnol., 70.","DOI":"10.1016\/j.bcab.2025.103828"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khan, M.F., Liao, J., Liu, Z., and Chugh, G. (2025). Bacterial Cytochrome P450 Involvement in the Biodegradation of Fluorinated Pyrethroids. J. Xenobiotics, 15.","DOI":"10.3390\/jox15020058"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3390\/jox11030007","article-title":"The Central Role of Cytochrome P450 in Xenobiotic Metabolism\u2014A Brief Review on a Fascinating Enzyme Family","volume":"11","author":"Esteves","year":"2021","journal-title":"J. Xenobiotics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1038\/s41559-017-0347-8","article-title":"Genome Expansion and Lineage-Specific Genetic Innovations in the Forest Pathogenic Fungi Armillaria","volume":"1","author":"Sipos","year":"2017","journal-title":"Nat. Ecol. Evol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"579","DOI":"10.12691\/jfnr-7-8-5","article-title":"Chemical, Mechanical, Antioxidant, and Antimicrobial Properties of Paper Prepared from Cocoa Bean Shell Using Polyethylene Glycol","volume":"7","author":"Tamrin","year":"2019","journal-title":"J. Food Nutr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129228","DOI":"10.1016\/j.foodchem.2021.129228","article-title":"Comparison of Characteristic Components in Tea-Leaves Fermented by Aspergillus pallidofulvus PT-3, Aspergillus sesamicola PT-4 and Penicillium manginii PT-5 Using LC-MS Metabolomics and HPLC Analysis","volume":"350","author":"Ma","year":"2021","journal-title":"Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"4","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate Transcript Quantification from RNA-Seq Data with or without a Reference Genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/bioinformatics\/btp612","article-title":"DEGseq: An R Package for Identifying Differentially Expressed Genes from RNA-Seq Data","volume":"26","author":"Wang","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ernst, J., and Bar-Joseph, Z. (2006). STEM: A tool for the analysis of short time series gene expression data. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-191"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/nar\/gkaf334","article-title":"antiSMASH 8.0: Extended gene cluster detection capabilities and analyses of chemistry, enzymology, and regulation","volume":"53","author":"Blin","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00019606-200603000-00009","article-title":"Validation of the 2-DeltaDeltaCt Calculation as an Alternate Method of Data Analysis for Quantitative PCR of BCR-ABL P210 Transcripts","volume":"15","author":"Arocho","year":"2006","journal-title":"Diagn. Mol. Pathol."},{"key":"ref_30","first-page":"297","article-title":"Biological characteristics of three Armillaria species from Northeast China and artificial cultivation of A. ostoyae","volume":"42","author":"Chen","year":"2023","journal-title":"Mycosystema"},{"key":"ref_31","unstructured":"Li, D. (2021). Cloning and Function Analysis of CYP82Ds Genes from Camellia sinensis. [Doctoral Dissertation, Zhejiang University]."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"020014","DOI":"10.1063\/5.0069616","article-title":"Biodegradation of Methylxanthines by Coniophora puteana","volume":"2429","author":"Jerman","year":"2021","journal-title":"AIP Conf. Proc."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"He, C., Huang, Y., Liu, P., Wei, J., Yang, Y., Xu, L., and Xiao, M. (2019). Transcriptome Analysis of Genes and Metabolic Pathways Associated with Nicotine Degradation in Aspergillus Oryzae 112822. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5446-2"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100938","DOI":"10.1016\/j.dwt.2024.100938","article-title":"Enhancing Fungal Adaptation for Efficient Caffeine Degradation in Wastewater: Biomimetic Approach and Environmental Optimization","volume":"321","author":"Dave","year":"2025","journal-title":"Desalination Water Treat."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Khan, M.F. (2025). Fungi for Sustainable Pharmaceutical Remediation: Enzymatic Innovations, Challenges, and Applications\u2014A Review. Processes, 13.","DOI":"10.3390\/pr13041034"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ran, L.-X., Wei, X.-Y., Ren, E.-F., Qin, J.-F., Rasheed, U., and Chen, G.-L. (2025). Application of Microbial Fermentation in Caffeine Degradation and Flavor Modulation of Coffee Beans. Foods, 14.","DOI":"10.3390\/foods14152606"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Khan, M.F., Hof, C., Niemcov\u00e1, P., and Murphy, C.D. (2023). Recent Advances in Fungal Xenobiotic Metabolism: Enzymes and Applications. World J. Microbiol. Biotechnol., 39.","DOI":"10.1007\/s11274-023-03737-7"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/12\/2720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:22:13Z","timestamp":1766499733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/12\/2720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["microorganisms13122720"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13122720","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]}}}