Comparative Metabolite Profiling and Bioactivity Evaluation of Pneumatophore-Derived Aspergillus Strains From Three Geographically Distinct Mangrove Ecosystems of India: Isolation of a New Dahejpyrone Derivative

Endophytic Paenibacillus lactis PEL6 from Mitrephora heyneana as a Source of Anti-Staphylococcus aureus Metabolites: In Vitro and In Silico Evaluation

Endophytic bacteria from medicinal plants are increasingly recognised as sources of antimicrobial metabolites. However, the endophytic bacterial community of Mitrephora heyneana remains poorly explored. In the present study, endophytic bacteria were isolated from the leaves of M. heyneana, collected from the Western Ghats of Tamil Nadu, India. Among seven isolates, the plant endophyte strain from leaf 6th strain (PEL6) was identified as Paenibacillus lactis through 16S rRNA gene sequencing. The ethyl acetate extract of PEL6 (EAE-PEL6) was subjected to gas chromatography–mass spectrometry (GC-MS) analysis, which putatively identified 32 metabolites based on GC-MS library matching, including pyrrolo [1,2-a] pyrazine-1,4-dione derivatives and triazole compounds as major constituents. The EAE-PEL6 demonstrated significant in vitro antibacterial activity against Staphylococcus aureus. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity), profiling predicted drug-likeness and pharmacokinetic properties of selected candidate compounds. Molecular docking suggested favourable binding of selected metabolites to S. aureus target proteins; however, these interactions require experimental validation. Density Functional Theory calculations indicated that CID 70504 had the lowest Highest Occupied Molecular Orbital (HOMO)–Lowest Unoccupied Molecular Orbital (LUMO) energy gap, reflecting higher electronic reactivity. Molecular electrostatic potential mapping further supported its enhanced binding propensity. Molecular dynamics simulations suggested structural stability, with Root Mean Square Deviation, Solvent Accessible Surface Area, radius of gyration, and hydrogen-bond analyses indicating stable interactions throughout the 100 ns trajectory. Overall, this study identifies P. lactis PEL6 as a promising endophytic source of anti-S. aureus metabolites and provides candidates for future purification, structural confirmation, and biological validation.

Morpho-molecular approach reveals a myco-endophyte, Aspergillus novoparasiticus CBS126849 (MTCC-13997) from the roots of Capparis decidua with therapeutic and enzymatic potential

Harnessing Penicillium chrysogenum metabolites for immune modulation and anti-inflammatory activity: chemical profiling, in vivo validation, and computational insights

Inflammation-driven disorders such as rheumatoid arthritis require safer and more effective therapeutic alternatives to conventional immunosuppressive drugs. In this study, we purified and identified a soil-derived fungal isolate. Its anti-inflammatory and anti-arthritic potential was evaluated using integrated chemical, biological, and computational approaches. Morphological characteristics combined with 18 S rRNA gene sequencing confirmed the isolate as Penicillium chrysogenum (GenBank accession: PV110187.1), validating its taxonomic identity for downstream investigations. Gas chromatography–mass spectrometry (GC–MS) profiling of the methanolic extract revealed a chemically diverse metabolome dominated by polyunsaturated fatty acid esters and terpenoid constituents. The most abundant constituents were methyl 5,8,11,14-eicosatetraenoate (43.21%), caryophyllene oxide (17.68%), and docosahexaenoic acid methyl ester (6.84%). Additionally, several other known anti-inflammatory metabolites—including costunolide, reynosin, lupeol, and valerenol—were also identified in the extract. In vitro evaluation demonstrated potent inhibition of heat-induced protein denaturation, with an IC₅₀ value of 10.07 ± 0.07 µg/mL, supporting strong anti-inflammatory activity. The IC₅₀ value guided the selection of rational in vivo doses. These were subsequently validated using a complete Freund’s adjuvant-induced arthritis model. Administration of the fungal extract at 10, 20, and 40 mg/kg significantly alleviated paw swelling in a dose-dependent manner. The highest dose exhibited efficacy comparable to methotrexate. Histopathological analyses confirmed marked preservation of joint cartilage, synovial architecture, and muscle integrity. Extract treatment restored the cytokine balance by significantly suppressing the pro-inflammatory cytokines IFN-γ, IL-1β, and IL-17. Conversely, levels of the anti-inflammatory cytokine IL-4 were markedly enhanced. Besides, biochemical assessments demonstrated hepatic and renal safety. Molecular docking studies supported these findings, revealing strong binding affinities of key metabolites to the JAK2 receptor. Therefore, these results support the potential of P. chrysogenum extract as a biologically active anti-inflammatory preparation, pending additional mechanistic and translational studies.

Marine-Derived Cladosporium sp. MBLC9-138 as a Source of Mycophenolic Acid with Preliminary Antibacterial Activity

Marine-derived fungi are important reservoirs of bioactive secondary metabolites, yet the diversity of fungal producers of mycophenolic acid (MPA) remains incompletely explored. In this study, 304 fungal strains were isolated from marine sediments collected from three coastal regions of Vietnam and screened for MPA production using thin-layer chromatography, high-performance liquid chromatography, and LC-MS confirmation. Twenty-five isolates (8.22%) were identified as MPA producers and were preliminarily assigned to the fungal genera Penicillium, Aspergillus, and Cladosporium, with two isolates remaining unidentified, based on morphological characteristics. Strain MBLC9-138 was selected for detailed characterization because it represented a non-Penicillium MPA-producing isolate assigned to Cladosporium. Morphological observations and multilocus sequence analyses based on internal transcribed spacer region (ITS), actin gene (ACT), and beta-tubulin gene (TUB/TUB2) supported its identification as Cladosporium sp. MBLC9-138. HPLC analysis showed that this strain produced 463.25 mg/L MPA after 5 days of cultivation in NaCl-supplemented potato dextrose broth, while the maximum yield reached 632.03 ± 2.39 mg/L at 168 ± 12 h during the late exponential to early stationary phase. The purified MPA extract inhibited Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, and Staphylococcus aureus ATCC 33591, with MIC values of 16, 32, and 64 µg/mL, respectively. These findings identify Cladosporium sp. MBLC9-138 as a previously underreported marine fungal source of MPA, expand the known taxonomic range of MPA-producing fungi, and support further strain optimization, metabolite purification, and antibacterial characterization.

Two new phomanolide-type meroterpenoids from the endophytic fungi Plenodomus sp. IQ-2000.

The genus Plenodomus remains relatively understudied, with limited reports regarding its specialized metabolites. In this study, the endophytic strain Plenodomus sp. IQ-2000, isolated from Tanacetum parthenium (L.) Schultz-Bip, was investigated following preliminary screenings that revealed a promising capacity to produce chemically diverse entities and inhibit human protein tyrosine phosphatase 1B (hPTP1B1-400). Using a strategy based on Feature-Based Molecular Networking (FBMN) integrated with the bioactivity of active fractions, five secondary metabolites (1-5) were prioritized and isolated. Their structures were elucidated through extensive NMR spectroscopy and high-resolution mass spectrometry (HRESIMS). Among the isolates, two undescribed phomanolide-type meroterpenoids, 7,8-epoxy-prephomanolide (1) and prephomanolide (2), are reported, whose absolute configuration were assigned via electronic circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) calculations. The isolation of 2 provides crucial experimental evidence for the previously hypothesized biosynthesis of this class of compounds. Compounds 2 and 3 exhibited moderate inhibitory potential against the evaluated target, with inhibition rates of 73.0 ± 3.5% and 51.5 ± 4.5% at 20 μg/mL, respectively. Notably, all isolated compounds are reported from the genus Plenodomus for the first time, expanding the known chemical space of this fungal genus.

Rare open-chain antifungal butenolides from an endophytic Aspergillus sp.: a GNPS molecular networking-guided isolation.

Chemical investigation of the endophytic fungus Aspergillus sp. FH-1 from Valeriana officinalis L., guided by GNPS molecular networking, afforded six compounds. These included two rare open-chain butenolides, designated as terrusnolides D (1) and F (2), together with four known analogues: terrusnolide A (3), versiol (4), decumbenone A (5), and decumbenone B (6). Their structures were unequivocally determined through extensive spectroscopic methods (HRESIMS, 1D/2D NMR, and ECD). Antifungal evaluation against the phytopathogen Colletotrichum gloeosporioides demonstrated that compounds 1 and 3 exhibited significant inhibitory activity, with EC50 values of 32.77 ± 1.12 μg/mL and 42.81 ± 1.01 μg/mL, respectively, both outperforming the positive control carbendazim.