Bioactive Secondary Metabolites from Fungi

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Cell Biology, Metabolism and Physiology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 18574

Special Issue Editor


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Guest Editor
1. Department Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
2. Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt
Interests: natural product chemistry; structure elucidation; NMR spectroscopy; neurodegenerative disorders; biofilm inhibition; antimicrobial
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Special Issue Information

Dear Colleagues,

Fungi are ubiquitous eukaryotic organisms that can accommodate a vast variety of ecosystems. They vary from being safe edible foods to medicinal mushrooms or sometimes highly toxic variants. From the latest count of the number of fungi on the planet, it was estimated that there are 1.5 million species, with only one-tenth of these explored so far. Therefore, fungal diversity is still a promising research topic. In this Special Issue, we aim to valorize fungal secondary metabolites with interesting bioactivity/bioactivities in terms of their antimicrobial, antiproliferative, anti-inflammatory, antioxidant, and antidiabetic properties, related neurodegenerative disorders, and others.

You are welcome to contribute to this Special Issue by submitting your research and/or review articles related to the topic of “Bioactive Secondary Metabolites from Fungi”. We look forward to receiving your valuable contributions.

Prof. Dr. Sherif S. Ebada
Guest Editor

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Keywords

  • fungal biodiversity
  • natural products
  • anti-infective
  • antibiotic resistance
  • biofilm inhibition
  • neurodegenerative disorders

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Published Papers (10 papers)

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Research

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21 pages, 2219 KB  
Article
Chemical and Biological Investigation of the Endophytic Aspergillus terreus (SU5) Inhabiting Date Fruits (Phoenix dactylifera)
by Ahmed Abdel-Hadi, Mohammed Alaidarous, Abdulrahman Alatiq, Yahya Madkhali, Saeed Banawas, Mohamed Abouelela and Abdallah Hassane
J. Fungi 2026, 12(4), 249; https://doi.org/10.3390/jof12040249 - 30 Mar 2026
Viewed by 710
Abstract
Endophytic fungi associated with date fruits (Phoenix dactylifera) are mostly under-explored, despite their potential as reservoirs of natural compounds. The aims of this study were to characterize the endophytic fungus Aspergillus terreus (SU5) isolated from date fruits, and to investigate its [...] Read more.
Endophytic fungi associated with date fruits (Phoenix dactylifera) are mostly under-explored, despite their potential as reservoirs of natural compounds. The aims of this study were to characterize the endophytic fungus Aspergillus terreus (SU5) isolated from date fruits, and to investigate its biological activities and chemical profile for the first time. Morphological and molecular methods were utilized to identify Aspergillus terreus. A liquid chromatography–mass spectrometry analysis (LC/MS/MS) was conducted to determine the chemical profile of the crude extract. Biological properties were investigated through acetylcholine esterase and butyrylcholine esterase inhibition, cytotoxicity assays against MCF-7 and MCF-7/Adr, and antioxidant assays. LC/MS/MS of the fungal extract resulted in the detection of 39 of established secondary metabolites, primarily comprising polyketides, quinones, and phenolic derivatives. The crude extract demonstrated significant antioxidant activity, especially in the ABTS assay (IC50 = 50.18 μg/mL), considerable cytotoxicity against MCF-7 breast cancer cells, diminished efficacy against the drug-resistant MCF-7/Adr cell line, and preferential inhibition of butyrylcholinesterase compared to acetylcholinesterase. While none of the identified compounds are novel, numerous metabolites are documented here for the first time from an endophytic A. terreus associated with date fruits. The findings underscore date fruits as a prospective ecological niche for a chemically varied endophytic fungus with potential pharmaceutical significance. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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23 pages, 4126 KB  
Article
Genome and Secondary Metabolites Analysis of Fusarium oxysporum BPF55 Associated with Blaps rynchopetera and Its Anti-MRSA Biofilm Potential
by Xiaolu Zhu, Haorong Yin, Dasong Yang and Yinhe Yang
J. Fungi 2026, 12(4), 236; https://doi.org/10.3390/jof12040236 - 25 Mar 2026
Viewed by 762
Abstract
Antimicrobial resistance (AMR) represents a critical global health challenge, with methicillin-resistant Staphylococcus aureus (MRSA) posing a significant threat in both hospital-acquired and community-associated infections. Research has demonstrated that biofilm formation is a key factor contributing to drug resistance in MRSA. In this study, [...] Read more.
Antimicrobial resistance (AMR) represents a critical global health challenge, with methicillin-resistant Staphylococcus aureus (MRSA) posing a significant threat in both hospital-acquired and community-associated infections. Research has demonstrated that biofilm formation is a key factor contributing to drug resistance in MRSA. In this study, we investigated an fungus, Fusarium oxysporum BPF55, isolated from Blaps rynchopetera, which inhibits MRSA biofilm formation. The aim of this research was to identify the fungal strain and comprehensively characterize its genomic features, as well as to evaluate its anti-MRSA biofilm potential. Whole-genome sequencing revealed a genome size of 50,097,681 base pairs, a GC content of 47.36%, and 16,507 predicted coding genes. AntiSMASH analysis identified 56 secondary metabolite biosynthetic gene clusters, including those involved in the synthesis of various natural products such as terpenes, non-ribosomal peptides, and polyketides. Using UPLC-MS/MS, 15 compounds were annotated from the ethyl acetate extract. Molecular docking studies demonstrated that four compounds exhibit varying affinities for SarA and AgrA, two key proteins involved in MRSA biofilm formation. Overall, these findings suggest that the fungus F. oxysporum BPA55 produces a variety of secondary metabolites and contains bioactive compounds with potential anti-MRSA biofilm activity. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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21 pages, 949 KB  
Article
Antimicrobial Activity of Submerged Cultures of Endophytic Fungi Isolated from Three Chilean Nothofagus Species
by Héctor Valenzuela, Daniella Aqueveque-Jara, Mauricio Sanz, Margarita Ocampo, Karem Henríquez-Aedo, Mario Aranda and Pedro Aqueveque
J. Fungi 2026, 12(1), 77; https://doi.org/10.3390/jof12010077 - 21 Jan 2026
Viewed by 846
Abstract
Endophyte fungi (EF) are considered a new and valuable reservoir of bioactive molecules of biotechnological interest for pharmacy, agricultural and forestry industries. In this study, thirty EFs, isolated from three Chilean Nothofagus species (N. alpina, N. dombeyi, N. oblicua) [...] Read more.
Endophyte fungi (EF) are considered a new and valuable reservoir of bioactive molecules of biotechnological interest for pharmacy, agricultural and forestry industries. In this study, thirty EFs, isolated from three Chilean Nothofagus species (N. alpina, N. dombeyi, N. oblicua) were identified and cultured in submerged liquid fermentations aimed at searching for natural active substances. The extracts obtained were evaluated against pathogenic bacteria and fungi. Sixteen extracts (53.3%) presented antibacterial and fourteen (46.6%) presented antifungal activities in different intensities. Extracts from isolates Coryneum sp.-72 and P. cinnamomea-78 exhibited the highest antimicrobial activity. Using bioautography, the compounds responsible for the antimicrobial activity exhibited by Coryneum sp.-72 and P. cinnamomea-78 were detected and characterized. Coryneum sp.-72 showed bactericidal properties at 200 μg/mL and bacteriostatic effects at 50 μg/mL against B. cereus, B. subtilis, L. monocytogenes and S. aureus. MIC values indicated that P. cinnamomea-78 exhibited a strong fungistatic and fungicidal effect against B. cinerea and C. gloesporioides at 10–50 μg/mL. Isolates were grouped in the following order: Botryosphaeriales, Diaporthales, Eurotiales, Helotiales, Hypocreales, Pleosporales, Magnaporthales, Sordariales and Polyporales. EF isolated, identified and evaluated constitute the first report for Chilean Nothofagus genus. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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13 pages, 9405 KB  
Article
Characterization of Antimicrobial Compounds from Trichoderma flavipes Isolated from Freshwater Environments
by Jeong Tae Kim, Won Su Cheon, Sanghee Lee, Jaeduk Goh, Chang Soo Lee and Hye Yeon Mun
J. Fungi 2025, 11(12), 857; https://doi.org/10.3390/jof11120857 - 2 Dec 2025
Cited by 2 | Viewed by 809
Abstract
Traditional antibiotic agents are commonly employed in the control of pathogenic microorganisms. However, there is a growing need for novel alternative antimicrobial agents owing to the increasing prevalence of resistance to these treatments. Freshwater fungi, recognized for producing diverse secondary metabolites with biological [...] Read more.
Traditional antibiotic agents are commonly employed in the control of pathogenic microorganisms. However, there is a growing need for novel alternative antimicrobial agents owing to the increasing prevalence of resistance to these treatments. Freshwater fungi, recognized for producing diverse secondary metabolites with biological activities, offer promising sources for drug development. However, studies on Trichoderma flavipes remain limited. Therefore, this study was conducted to investigate the antimicrobial properties of bioactive compounds derived from Trichoderma flavipes FBCC-F1632, a fungal species isolated from freshwater environments in Korea. The fungal strain FBCC-F1632 was isolated from stream soil obtained from Mungyeon-si, Republic of Korea, and identified through DNA extraction and phylogenetic analysis. Antimicrobial activity against Staphylococcus aureus and Bacillus cereus was assessed, revealing significant inhibitory rates. Potential bioactive compounds were extracted, purified, and structurally characterized using chromatographic and spectroscopic techniques, including nuclear magnetic resonance and mass spectrometry. Five bioactive compounds were identified: F1632-1 (cordyol C), F1632-2 (diorcinol), F1632-3 (violaceol I), F1632-4 (tryptophol), and F1632-6 (violaceol II). These compounds exhibited notable antimicrobial activities, particularly against Staphylococcus aureus and Bacillus cereus, underscoring their potential as candidates for the development of novel antimicrobial therapeutics. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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20 pages, 8423 KB  
Article
Transcription Factors AsMYB1 and AsMYB3 Regulate Betalain Biosynthesis in Aspergillus sydowii H-1
by Yulu Ran, Yu Cao, Yihan Guo, Jie Zeng, Jiale Wang, Dongyou Xiang, Hui Xu and Yi Cao
J. Fungi 2025, 11(11), 793; https://doi.org/10.3390/jof11110793 - 6 Nov 2025
Viewed by 944
Abstract
Betalains are nitrogen-containing pigments found only in Caryophyllales plants and a few Basidiomycetes; no Ascomycota species have been found to contain them. Here, global untargeted metabolomics analysis revealed that the violet pigment generated by the ascomycete Aspergillus sydowii H-1 under standard conditions of [...] Read more.
Betalains are nitrogen-containing pigments found only in Caryophyllales plants and a few Basidiomycetes; no Ascomycota species have been found to contain them. Here, global untargeted metabolomics analysis revealed that the violet pigment generated by the ascomycete Aspergillus sydowii H-1 under standard conditions of cultivation contains six distinct betalains compounds. Genetic analysis revealed tyrosinase (AsTYRs) and DOPA 4,5-dioxygenase (AsDODA1) as key enzymes essential for the synthesis of both the violet pigment and betalains. In addition, AsTYRs and AsDODA1 were found to regulate hyphal development and branching, mycelial pellet compactness, redox homeostasis, and stress responses, all of which had a significant impact on A. sydowii H-1 secondary metabolism. Crucially, two MYB transcription factors, AsMYB1 and AsMYB3, were identified to be negative regulators of violet pigment synthesis. Deletion of AsMYB1 or AsMYB3 boosted pigment yield by 6.7 and 7.3 times, respectively, and increased betalain accumulation, whereas overexpressing them completely eliminated pigment production. Yeast one-hybrid assays and luciferase reporter assays revealed AsMYB1 and AsMYB3 directly bind to the promoters of AsTYR1 and AsTYR2 to suppress the synthesis of betalains and the violet pigment. Our study reported the first betalain-producing ascomycete species and elucidated the molecular basis of its pigment regulation, providing valuable insights for the microbial synthesis of natural colorants. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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17 pages, 7377 KB  
Article
Comparative Untargeted Metabolomic Analysis of Fruiting Bodies from Three Sanghuangporus Species
by Zixuan Jiang, Shimao Chen, Jia Song, Tao Xie, Yu Xue and Qingshan Yang
J. Fungi 2025, 11(8), 558; https://doi.org/10.3390/jof11080558 - 28 Jul 2025
Cited by 3 | Viewed by 1496
Abstract
Sanghuangporus spp. are medicinal fungi with significant therapeutic value, but their taxonomic ambiguity and frequent market adulteration have hindered their standardized utilization. In this study, untargeted metabolomics based on UPLC-Q-TOF-MS was employed to systematically analyze the metabolic profiles of three Sanghuangporus species: Sanghuangporus [...] Read more.
Sanghuangporus spp. are medicinal fungi with significant therapeutic value, but their taxonomic ambiguity and frequent market adulteration have hindered their standardized utilization. In this study, untargeted metabolomics based on UPLC-Q-TOF-MS was employed to systematically analyze the metabolic profiles of three Sanghuangporus species: Sanghuangporus. sanghuang (SS), Sanghuangporus. vaninii (SV), and Sanghuangporus. baumii (SB). A total of 788 metabolites were identified and classified into 16 categories, among which 97 were common differential metabolites, including bioactive compounds such as flavonoids, polysaccharides, and terpenoids. Multivariate statistical analyses (PCA and OPLS-DA) revealed distinct metabolic patterns among the species. KEGG pathway enrichment analysis showed that the differential metabolites were mainly involved in flavonoid and isoflavonoid biosynthesis. Notably, SV and SB exhibited significantly higher levels of several key bioactive compounds, including Apigenin and D-glucuronolactone, compared to SS. These findings highlight substantial interspecies differences in metabolic composition and pharmacological potential, providing a scientific basis for species authentication, quality control, and medicinal development of Sanghuangporus. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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14 pages, 3533 KB  
Article
New Chaetoglobosins with Fungicidal Activity from Chaetomium sp. UJN-EF006 Endophytic in Vaccinium bracteatum
by Luo-Jing Wang, Zong-Yan Ma, Xin-Ling Wang, Kai-Le Wang, Tong Zhang, Rui-Ying Han, Jun-Jiang Li, Jie Bao, Yin-Yin Wang and Hua Zhang
J. Fungi 2025, 11(7), 511; https://doi.org/10.3390/jof11070511 - 7 Jul 2025
Cited by 4 | Viewed by 1544
Abstract
Nine chaetoglobosins (19) including five previously undescribed ones (15) were obtained from the culture broth of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these [...] Read more.
Nine chaetoglobosins (19) including five previously undescribed ones (15) were obtained from the culture broth of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites were elucidated by spectroscopic methods including mass spectroscopy, nuclear magnetic resonance, single crystal X-ray crystallography, and electronic circular dichroism. To accelerate the development of novel fungicides, all of the isolated chaetoglobosins were evaluated for their antifungal activity against two crop pathogens, Botrytis cinerea and Sclerotinia sclerotiorum. The assay results revealed that chaetoglobosins 2, 6, 7, and 9 possessed a significant fungicidal effect against B. cinerea, with EC50 values all below 10 μg/mL. Particularly, the most potent compound, 7, was 175- and 96-fold as active as the commercially available fungicides carbendazim (EC50 70.11 μg/mL) and azoxystrobin (EC50 39.02 μg/mL), respectively. A further observation under scanning electron microscope indicated that compound 2 could markedly impair the fungal hyphae of B. cinerea. The study demonstrates that the chaetoglobosins had excellent in vitro antifungal activities against B. cinerea. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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28 pages, 2549 KB  
Article
Exploring the Bioactive Secondary Metabolites of Two Argentine Trichoderma afroharzianum Strains
by Rodrigo José Nunes Calumby, Antonella Santone, Estefanía Butassi, Laura Andrea Svetaz, Márcia de Souza Carvalho Melhem, Sebastián Pablo Rius and Valeria Alina Campos-Bermudez
J. Fungi 2025, 11(6), 457; https://doi.org/10.3390/jof11060457 - 17 Jun 2025
Cited by 2 | Viewed by 2573
Abstract
Trichoderma spp. produce diverse secondary metabolites with biological activity. This study explored the antimicrobial, antibiofilm, antioxidant, and cytotoxic properties of metabolites from two native Trichoderma strains, 10BR1 and UEPA AR12, isolated from rhizospheric soils. Organic extracts from both strains demonstrated broad-spectrum antimicrobial activity, [...] Read more.
Trichoderma spp. produce diverse secondary metabolites with biological activity. This study explored the antimicrobial, antibiofilm, antioxidant, and cytotoxic properties of metabolites from two native Trichoderma strains, 10BR1 and UEPA AR12, isolated from rhizospheric soils. Organic extracts from both strains demonstrated broad-spectrum antimicrobial activity, inhibiting Gram-positive and Gram-negative bacteria, as well as various Candida species, with notable efficacy against Staphylococcus aureus (MICs: 15.6–31.25 µg/mL). The extracts also showed antibiofilm activity, with UEPA AR12 exhibiting the highest inhibition against Escherichia coli (81.8%), Enterococcus faecalis (92.8%), Candida albicans (87.9%), and Candida parapsilosis (89.3%). Antioxidant activity, assessed via DPPH assay, revealed a dose-dependent radical scavenging effect (12.88% to 39.67% at 7.8–1000 µg/mL). Cytotoxicity assays indicated that UEPA AR12 extracts were more cytotoxic (IC50: 202.5–234.3 µg/mL) than 10BR1 (IC50: 368.7–602.1 µg/mL) in non-tumor cells, with similar trends in tumor cells (Huh7). HPLC/MS analysis identified 21 metabolites in the extracts. Genomic analyses, supported by rpb2 gene and phylogenetic clustering, confirmed that both strains were T. afroharzianum. FUNGISMASH revealed multiple biosynthetic gene clusters, predominantly Type I polyketide synthase (T1PKS). Additionally, targeted genomic analyses did not detect mycotoxin-related genes. These findings highlight the antimicrobial, antibiofilm, and antioxidant potentials of these strains, positioning them as sources of bioactive metabolites for pharmaceutical applications. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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Review

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31 pages, 2867 KB  
Review
A Comprehensive Review on Chemical Structures and Bioactivities of Ostropomycetidae Lichens
by Yunhui Wang, Chengyue Hao, Shuhao Jiang, Yanhu Ju, Wei Li and Zefeng Jia
J. Fungi 2025, 11(5), 369; https://doi.org/10.3390/jof11050369 - 9 May 2025
Cited by 2 | Viewed by 3419
Abstract
Lichenized fungi, recognized as an ecologically vital and pharmaceutically promising resource, hold substantial value in both environmental conservation and medicinal applications. As the second largest subclass within the lichen-forming fungi of Lecanoromycetes, Ostropomycetidae emerged as a critical reservoir of bioactive secondary metabolites. Current [...] Read more.
Lichenized fungi, recognized as an ecologically vital and pharmaceutically promising resource, hold substantial value in both environmental conservation and medicinal applications. As the second largest subclass within the lichen-forming fungi of Lecanoromycetes, Ostropomycetidae emerged as a critical reservoir of bioactive secondary metabolites. Current research has revealed that these secondary metabolites demonstrate remarkable bioactivities, positioning them as potential sources for novel pharmaceutical compounds. Despite considerable progress in characterizing chemical constituents and evaluating bioactivities within this subclass, a systematic summary of these discoveries remains absent. This review synthesizes the lichenochemical research progress, providing critical evaluations of 202 structurally characterized compounds from Ostropomycetidae lichen species over recent decades. These Ostropomycetidae-derived compounds cover the phenols, polyketides, fatty acids, terpenoids, steroids, and non-ribosomal peptides, and exhibit diverse bioactivities including antitumor, anti-inflammatory, antibacterial, antifungal, antiviral, antioxidant, anti-angiogenic, anti-neurodegenerative diseases, antitubercular, anti-herbivore, and antitrypanosomal, and so on. The aim of this review is to establish a robust chemodiversity framework and to offer strategic guidance for targeted exploration of lichen-derived drug candidates in the biological resources of Ostropomycetidae lichens. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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46 pages, 3153 KB  
Review
Unveiling the Bioactive Compounds and Therapeutic Potential of Russula: A Comprehensive Review
by Jingya Yang, Samantha C. Karunarathna, Nimesha Patabendige, Entaj Tarafder, Dengji Lou, Yuanqing Zhou and Kalani Hapuarachchi
J. Fungi 2025, 11(5), 341; https://doi.org/10.3390/jof11050341 - 27 Apr 2025
Cited by 7 | Viewed by 4578
Abstract
Russula, a genus of Basidiomycetes with considerable taxonomic diversity, holds significant potential in both traditional and modern medicinal practices. This comprehensive review explores the bioactive compounds identified in various Russula species, detailing their characterization, structural elucidation, and classification. The medicinal properties of [...] Read more.
Russula, a genus of Basidiomycetes with considerable taxonomic diversity, holds significant potential in both traditional and modern medicinal practices. This comprehensive review explores the bioactive compounds identified in various Russula species, detailing their characterization, structural elucidation, and classification. The medicinal properties of these fungi are examined, with a focus on their antioxidant, anti-inflammatory, and immunomodulatory effects, supported by both historical usage and contemporary preclinical pharmacological research. The review also highlights emerging biotechnological applications including environmental remediation, antimicrobial agents, and functional food development. Safety and toxicological considerations are evaluated to provide a balanced perspective on the medicinal use of Russula. The review concludes by summarizing the key findings and emphasizing the importance of Russula in both traditional medicine and future clinically validated innovations. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites from Fungi)
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