Search Results (56)

The emergence of antimicrobial resistance and the increasing incidence of cancer have highlighted the urgent need to develop new drugs; therefore, the discovery of new bioactive molecules is an important goal for future research. In this study, freshwater fungi isolated from submerged Phragmites australis from Egypt were screened for antimicrobial and cytotoxic activities. Using ITS1 and ITS4 primers, eight frequently occurring Sordariomycetes taxa were identified and were then selected for further evaluation of bioactivity. Ethyl acetate crude extracts (A–H) were evaluated for antimicrobial activity using the agar disk-diffusion method. Extracts A and E, derived from Chaetomium globosum SCUF0000404 (PX596738) and Chaetomium madrasense SCUF0000401 (PX596735), respectively, showed broad-spectrum activity at 100 mg/mL against bacterial pathogens, including Staphylococcus aureus ATCC 29213 (15.33 and 18.00 mm), Streptococcus pyogenes ATCC 19615 (11.00 mm), Escherichia coli ATCC 35218 (10.33 and 10.67 mm), Klebsiella pneumoniae ATCC 700603 (14.00 and 16.67 mm), and Pseudomonas aeruginosa ATCC 27853 (13.33 and 16.33 mm), and show antifungal activity against Candida albicans ATCC 14053 (20.33 mm), Candida krusei ATCC 6258 (15.67 and 15.33 mm), Trichosporon asahii AMS 187 (17.00 and 17.67 mm), Exserohilum rostratum AMS 1077 (34.00 and 33.67 mm), and Trichophyton indotineae AMS 180 (38.33 and 34.00 mm). Selective cytotoxic effects on the breast cancer cell line MDA-MB-231 were observed by extracts A and E at IC₅₀ = 309 and 277 μg/mL, while non-selective cytotoxic effects on the normal HUVEC cell line were found with IC₅₀ = 919 and 796 μg/mL, respectively. Characterization of the most effective extracts A and E by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) shows that they have a wide range of secondary metabolites, including cytochalasans, azaphilone alkaloids, steroids, terpenoids, flavonoids, and phenols. These findings underscore the chemical diversity and therapeutic potential of freshwater fungi from Egypt. Full article

Fungal pigments have gained attention as eco-friendly and versatile materials for green nanotechnology because of their varied chemical structures, inherent redox properties, and strong metal ion-binding capabilities. These pigments, such as polyketides, azaphilones, melanins, and carotenoids, can function simultaneously as reducing, capping, and surface-functionalizing agents, facilitating the environmentally friendly production of metallic nanoparticles without the use of harmful chemicals. This review provides a critical overview of recent progress in the production, extraction, and application of fungal pigments for nanoparticle synthesis, focusing on the mechanistic roles of pigment functional groups in metal ion reduction, nanoparticle nucleation, growth, and stabilization. The impact of pigment chemistry and reaction conditions on the nanoparticle size, shape, crystallinity, and colloidal stability was thoroughly examined. Additionally, this review highlights the emerging biomedical, environmental, and industrial applications of pigment-mediated nanoparticles, emphasizing their biocompatibility and functional adaptability. Key challenges, such as variability in pigment yield and composition, limited mechanistic validation, lack of standardized synthesis protocols, and insufficient toxicity assessment, are critically analyzed in this review. Finally, future directions are outlined, emphasizing the importance of process optimization, omics-guided pigment discovery, and comprehensive safety evaluations as crucial steps toward the scalable and reliable use of fungal pigment-mediated nanoparticle synthesis in sustainable nanotechnology. Full article

Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the marine-derived fungus Penicillium sclerotiorum E23Y-1A by deleting the pathway-specific regulator gene A00667. HPLC analysis revealed the emergence of new metabolite peaks in the mutant strain Δ667 compared to the wild type. Subsequent purification yielded seven compounds: the mutant produced two novel meroterpenoids sclerotilins A and B (1 and 2) along with the known steroids ergosta-5,7,22-trien-3β-ol (3) and cerevisterol (4), while the wild type yielded the known steroid (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (5) and two azaphilones geumsanol G (6) and 5-chloro-3-[(1E,3R,4R,5S)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7R,8R,8aS)-6H-2-benzopyran-6-one (7). Bioactivity assays showed that compound 6 exhibited moderate antimicrobial activity against Staphylococcus aureus, and compound 3 displayed moderate cytotoxicity against five human cancer cell lines. These results demonstrate that A00667 is essential for azaphilone biosynthesis and that its disruption leads to the production of structurally distinct natural products, highlighting the potential of pathway engineering to redirect fungal metabolism to yield novel natural products. Full article

Monascus spp. are renowned for producing valuable Monascus azaphilone pigments (MonAzPs), yet their biosynthesis is intrinsically linked to the co-production of the mycotoxin citrinin, posing a significant safety challenge and limiting industrial application. Conventional approaches to disrupt citrinin synthesis often inadvertently reduce MonAzPs yield. To circumvent this limitation, we employed a dual-targeting strategy in Monascus ruber. In this study, we selected the mresa1-overexpressed strain—which can produce more MonAzPs and citrinin—as wild strain to construct a pksCT-deleted strain and explore whether pksCT deletion can affect the enhancement of MonAzPs caused by MrEsa1 overexpression. The results showed that the growth, development, and production of MonAzPs in △pksCT-M7::PtrpC-mresa1 were comparable to those in M7::PtrpC-mresa1, showing accelerated growth and higher MonAzPs yields than in M7. In addition, the relative expression levels of genes involved in MonAzPs synthesis in △pksCT-M7::PtrpC-mresa1 and M7::PtrpC-mresa1 showed the same trend compared with M7, indicating that MrEsa1 overexpression can resist the reduction in MonAzPs caused by pksCT deletion. This study establishes a novel and effective paradigm for decoupling desirable metabolite production from toxin synthesis in fungi, providing a strategic framework for the safe and enhanced production of MonAzPs. Full article

This study investigated the potential of the deep-sea-derived fungal metabolite, chlorinated azaphilone compound chaetomugilin O, in the treatment of thyroid cancer. Chaetomugilin O was extracted from the fungus Chaetomium globosum YP-106 and subjected to in vitro experiments. The results demonstrated that this compound significantly inhibited the proliferation of thyroid cancer CAL-62 cells in a dose-dependent manner, with an IC₅₀ value of 13.57 µM. Further mechanistic studies revealed that chaetomugilin O exerts its antitumor effects by inducing reactive oxygen species (ROS) accumulation, G2/M phase cell cycle arrest, and apoptosis. Transcriptomic analysis indicated its regulatory role in the PI3K-Akt signaling pathway, suggesting a multi-target synergistic antitumor mechanism. Molecular docking confirmed that chaetomugilin O binds to the Akt protein, forming a hydrogen bond with Lys158, implying its potential to directly inhibit Akt activity and interfere with PI3K-Akt pathway function. This study provides experimental evidence for the development of novel, low-toxicity, highly effective therapeutic agents for thyroid cancer. Full article

Six new alkaloid compounds, including two rare aromatic nitrile compounds talaronitriles A–B (1–2), a novel oxime-functionalized azadiphilone analogue talarooxime A (3), a new phenylhydrazone alkaloid talarohydrazone E (4), and two new dipeptide compounds talarodipeptides A–B (5–6), were isolated from the deep-sea cold-seep-derived fungus Talaromyces amestolkiae HDN21-0307 via OSMAC approach. Compound 1 is the first natural naphthalene compound with cyano groups. Compound 3 represents the first natural product containing an oxime-functionalized azadiphilone scaffold. Their structures and absolute configurations were elucidated through spectroscopic data analysis and quantum chemical calculations. Notably, compound 3 demonstrated moderate DPPH free-radical-scavenging activity, with an IC₅₀ value of 29.41 μM. Full article

Monascus purpureus is a filamentous fungus known for producing pharmaceutically valuable secondary metabolites, including azaphilone pigments and lovastatin. Lovastatin is an HMG-CoA reductase inhibitor widely used to manage hypercholesterolaemia, while Monascus pigments serve as natural colourants with antioxidant and antimicrobial properties. This study evaluated the impact of quorum-sensing molecules (QSMs)—tyrosol (0.3 mM), farnesol (0.2 mM) and linoleic acid (0.4 mM)—on pigment and lovastatin yields in shake flasks and 2.5 L stirred-tank bioreactors. QSMs were introduced 48 h post-inoculation in shake flasks and 24 h in bioreactors. All QSMs increased yellow (OD₄₀₀), orange (OD₄₇₀), and red (OD₅₁₀) pigments and lovastatin concentration relative to the control, with scale-up further enhancing yields. Farnesol produced the most pronounced effect: in flasks, OD₄₀₀ 7.10 (1.86-fold), OD₄₇₀ 8.00 (2.12-fold), OD₅₁₀ 7.80 (2.08-fold), and 74.6 mg/L lovastatin (2.05-fold); in bioreactors, OD₄₀₀ 11.9 (2.06-fold), OD₄₇₀ 15.1 (2.71-fold), OD₅₁₀ 13.7 (2.47-fold), and 97.2 mg/L lovastatin (2.48-fold). This was followed by tyrosol treatment and then linoleic acid. These findings demonstrate that QSMs—particularly farnesol—significantly (p < 0.01) stimulate pigment and lovastatin biosynthesis in M. purpureus. Quorum sensing modulation represents a promising, scalable strategy to optimise fungal fermentation for industrial metabolite production. Full article

The increasing global prevalence of hyperuricemia (HUA), particularly among younger populations, underscores the urgent need for safe and effective dietary interventions. Monascus fungi, long utilized in East Asian food culture, ferment rice to produce red yeast rice (RYR), a functional food rich in monacolin K and Monascus pigments. Among these, Monascus yellow pigments (MYPs)—natural azaphilone compounds used as food additives and colorants—have shown antioxidant, anti-inflammatory, and metabolic regulatory activities. However, their potential to alleviate hyperuricemia remains unexplored. This study investigates the urate-lowering and organ-protective effects of MYPs through a combination of in vitro, in vivo, and gut microbiota analyses. MYPs exhibited significant xanthine oxidase (XOD) inhibitory activity, and molecular docking confirmed that monascin (MS) and ankaflavin (AK) competitively bind to the XOD active site. In a murine HUA model, MYPs significantly reduced serum uric acid (SUA) levels without causing hepatic or renal toxicity. Mechanistically, MYPs downregulated renal UA reabsorption transporters (URAT1, GLUT9) and upregulated the excretory transporter ABCG2, enhancing uric acid (UA) excretion. These findings highlight MYPs as promising food-derived bioactives with dual XOD inhibition and uricosuric effects, offering a novel nutraceutical strategy for hyperuricemia prevention and management. Full article

Monascus purpureus is a filamentous fungus renowned for producing bioactive secondary metabolites, including lovastatin and azaphilone pigments. Lovastatin is valued for its cholesterol-lowering properties and cardiovascular benefits, while Monascus pigments exhibit anti-cancer, anti-inflammatory, and antimicrobial activities, underscoring their pharmaceutical and biotechnological relevance. This study evaluated the impact of carbohydrate-derived elicitors—mannan oligosaccharides, oligoguluronate, and oligomannuronate—on the enhancement of pigment and lovastatin production in M. purpureus C322 under submerged fermentation. Elicitors were added at 48 h in shake flasks and 24 h in 2.5 L stirred-tank fermenters. All treatments increased the production of yellow, orange, and red pigments and lovastatin compared to the control, with higher titres upon scale-up. OG led to the highest orange pigment yield (1.2 AU/g CDW in flasks; 1.67 AU/g CDW in fermenters), representing 2.3- and 3.0-fold increases. OM yielded the highest yellow and red pigments (1.24 and 1.35 AU/g CDW in flasks; 1.58 and 1.80 AU/g CDW in fermenters) and the highest lovastatin levels (10.46 and 12.6 mg/g CDW), corresponding to 2.03–3.03-fold improvements. These results highlight the potential of carbohydrate elicitors to stimulate metabolite biosynthesis and facilitate scalable optimisation of fungal fermentation. Full article

The long-term coexistence of sea cucumber-associated microorganisms with their host enables them to jointly withstand the unique marine ecological environment, and possess great potential for producing various natural products. However, under conventional laboratory conditions, most biosynthetic gene clusters (BGCs) in these microorganisms remain silent, necessitating the establishment of effective activation strategies for exploring bioactive secondary metabolites (SMs). Histone acetylation status regulates chromatin structure and plays a crucial role in cellular physiology and fungal secondary metabolism. Penicillium sclerotiorum SD-36 was isolated from sea cucumbers in our previous study. Genome sequencing results indicate that this strain harbors as many as 52 BGCs, suggesting it holds a wealth of genetic resources essential for synthesizing diverse SMs. Here, we describe the impact of a class 1 histone deacetylase (HDAC), PsHos2, on secondary metabolism of sea cucumber-associated Penicillium sclerotiorum SD-36. The colony morphology and SM profile of ΔPsHos2 exhibited significant changes, with the emergence of multiple new compound peaks. Six compounds, including five azaphilones, which are characterized by a pyranoquinone core structure, were isolated from ΔPsHos2, and seventeen unreported potential azaphilone-related nodes were obtained using molecular networking based on LC-MS/MS. Transcriptome analysis revealed that PsHos2 influenced the expression of 44 BGC core genes. Specifically, seven genes within cluster 86.1, the putative BGC for azaphilones, were upregulated, including two polyketide synthase (PKS) genes. The results indicate that regulation based on class 1 HDACs is an important strategy for enhancing SM synthesis in sea cucumber-associated fungi and expanding the resources of marine natural products. Full article

Monascus, a genus of fungi known for its fermentation capability and production of bioactive compounds, such as Monascus azaphilone pigments and Monacolin K, have received considerable attention because of their potential in biotechnological applications. Understanding the genetic basis of these metabolic pathways is crucial for optimizing the fermentation and enhancing the yield and quality of these products. However, Monascus spp. are not model fungi, and knowledge of their genetics is limited, which is a great challenge in understanding physiological and biochemical phenomena at the genetic level. Since the first application of particle bombardment to explore gene function, it has become feasible to link the phenotypic variation and genomic information on Monascus strains. In recent decades, accurate gene editing assisted by genomic information has provided a solution to analyze the functions of genes involved in the metabolism and development of Monascus spp. at the molecular level. This review summarizes most of the genetic manipulation tools used in Monascus spp. and emphasizes Agrobacterium tumefaciens-mediated transformation and nuclease-guided gene editing, providing comprehensive references for scholars to select suitable genetic manipulation tools to investigate the functions of genes of interest in Monascus spp. Full article

Subjecting the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A–C (1–3), along with the known analogue coelomycin (4), as well as a new azaphilone, noonaphilone A (5). Structures were assigned to 1–5 on the basis of a detailed spectroscopic analysis, and in the case of 1–2, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for 1–4, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, 2 incorporates a rare meta-Tyr motif, typically only reported in a limited array of Streptomyces metabolites. Similarly, a plausible biosynthetic pathway is proposed for 5, highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7R noonaphilone A (5) versus the 7S deflectin 1a (6). Full article

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1–3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5–17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 μM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 μg/mL to 256 μg/mL. Full article

Co-cultivation, coupled with the OSMAC approach, is considered an efficient method for expanding microbial chemical diversity through the activation of cryptic biosynthetic gene clusters (BGCs). As part of our project aiming to discover new fungal metabolites for crop protection, we previously reported five polyketides, the macrolides dendrodolides E (1) and N (2), the azaphilones spiciferinone (3) and 8α-hydroxy-spiciferinone (4), and the bis-naphtho-γ-pyrone cephalochromin (5) from the solid Potato Dextrose Agar (PDA) co-culture of two marine sediment-derived fungi, Plenodomus influorescens and Pyrenochaeta nobilis. However, some of the purified metabolites could not be tested due to their minute quantities. Here we cultivated these fungi (both axenic and co-cultures) in liquid regime using three different media, Potato Dextrose Broth (PDB), Sabouraud Dextrose Broth (SDB), and Czapek-Dox Broth (CDB), with or without shaking. The aim was to determine the most ideal co-cultivation conditions to enhance the titers of the previously isolated compounds and to produce extracts with stronger anti-phytopathogenic activity as a basis for future upscaled fermentation. Comparative metabolomics by UPLC-MS/MS-based molecular networking and manual dereplication was employed for chemical profiling and compound annotations. Liquid co-cultivation in PDB under shaking led to the strongest activity against the phytopathogen Phytophthora infestans. Except for compound 1, all target compounds were detected in the co-culture in PDB. Compounds 2 and 5 were produced in lower titers, whereas the azaphilones (3 and 4) were overexpressed in PDB compared to PDA. Notably, liquid PDB co-cultures contained meroterpenoids and depside clusters that were absent in the solid PDA co-cultures. This study demonstrates the importance of culture regime in BGC regulation and chemical diversity of fungal strains in co-culture studies. Full article

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3–6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum. Full article