{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:06:46Z","timestamp":1787684806189,"version":"build-2784847793"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Minzu University","award":["2019KJQD15"],"award-info":[{"award-number":["2019KJQD15"]}]},{"name":"Education Department of Guangxi","award":["202410608007"],"award-info":[{"award-number":["202410608007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Filamentous fungi exhibit high heavy metal resistance; elucidating their resistance mechanisms is of practical importance for fungal utilization and for engineering other microorganisms. However, the molecular basis of copper tolerance in filamentous fungi remains poorly understood, with few studies addressing this specific trait. Previously, we isolated a copper-hyper-resistant strain, P. janthinellum GXCR, and generated two mutagenized derivatives, EC-6 and UC-8. To investigate copper resistance, wild-type GXCR (WT) and mutants EC-6 and UC-8 were subjected to integrated physiological, biochemical, and transcriptomic analyses. Copper tolerance followed the rank order: WT &gt; UC-8 &gt; EC-6. Supplementation with Mn2+ or exogenous proline enhanced copper resistance. Under copper stress, intracellular reactive oxygen species (ROS) levels increased in all strains, correlating dynamically with activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as malondialdehyde (MDA) content, with all exhibiting a biphasic response: an initial rise followed by a decline with increasing Cu2+ concentration. WT accumulated less Cu and Cd but more Cr (at high concentration) than the mutants. In contrast, intracellular Pb accumulation in all three strains decreased monotonically with rising Pb doses. RNA-seq of WT and EC-6 grown in TYB with 0, 0.5 and 3 mM Cu2+ identified 8 copper-resistance-related genes, verified by real-time quantitative reverse transcription PCR (RT-qPCR). Weighted gene co-expression network analysis (WGCNA) clustered genes into 10 modules; integrating physiological data identified 10 traits, and the four most correlated modules yielded 116 hub genes mostly linked to energy metabolism, cell components and transporters. copA and ATP7, encoding Cu2+-exporting ATPases, were identified as central regulators of copper homeostasis and key contributors to enhance copper tolerance. These findings provide molecular insights into copper resistance of filamentous fungi and valuable genetic targets for rational strain engineering.<\/jats:p>","DOI":"10.3390\/ijms27073290","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:06:21Z","timestamp":1775441181000},"page":"3290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptome-Based WGCNA Reveals Hub Genes Involved in Copper Resistance of Penicillium janthinellum GXCR"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9290-9674","authenticated-orcid":false,"given":"Qin","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9217-4373","authenticated-orcid":false,"given":"Shaoke","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar","family":"Khan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Life Science and Technology, Guangxi University, 100 Daxue Road, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiman","family":"Gan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, 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, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-4012","authenticated-orcid":false,"given":"Yongqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlin","family":"Teng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyan","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0238-8835","authenticated-orcid":false,"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Marine Microbial Resources Industrialization Engineering Technology Research Center, School of Marine Sciences and Biotechnology, Guangxi Minzu University, 158 University Road, Nanning 530008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-1983","authenticated-orcid":false,"given":"Xiaoling","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Non-Food Biomass Energy Technology, Guangxi Academy of Sciences, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Present pollution status and safe utilization technologies of heavy metal-polluted farmland soil: A review","volume":"56","author":"Yu","year":"2024","journal-title":"Soils"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101653","DOI":"10.1016\/j.jksus.2021.101653","article-title":"Health and environmental effects of heavy metals","volume":"34","author":"Zaynab","year":"2022","journal-title":"J. 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