Epigenetic Activation of Silent Pathways in Endophytic Aspergillus sp. EGP214 Reveals Porphyrin-Derived Antimicrobial Metabolites Targeting DNA Gyrase: In Vitro and In Silico Evaluation.

Enhancing 3-O-methylfunicone production by endophytic Talaromyces pinophilus J6 through culture optimization and its anti-Helicobacter pylori activity

It is demonstrated that culture optimization is an efficient biotechnological strategy to improve 3O-methylfunicone production and support the further investigation of this compound as a scaffold for anti-H.

A metabolomics approach to target the effect of histone protein methyltransferase-specific probe UNC1999 on cryptic metabolites in an endophytic fungus Xylaria papulis Lloyd

Xylaria papulis Lloyd, an endophytic fungus, was isolated from the stem of Andrographis paniculata Willd., commonly known as green chiretta, which is native to India and Sri Lanka. To date, no report is available on the epigenetic modulation of X. papulis using the histone methyltransferase inhibitor UNC1999. Hence, this study aims to evaluate the independent effect of this probe. The fungal culture was evaluated for antioxidant (2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical scavenging assays) and antibacterial potential against six human pathogens: Staphylococcus epidermidis (ATCC 12223), methicillin-susceptible Staphylococcus aureus (MSSA) (ATCC 25923), methicillin-resistant Staphylococcus aureus (MRSA) (MU50), Enterobacter cloacae (ATCC 13047), Klebsiella pneumoniae (ATCC 700603), and E. coli (ATCC 25922). The crude extract, which was recovered from the samples treated with 250 nM of UNC1999, exhibited enhanced antioxidant and antibacterial efficacy against S. epidermidis (ATCC 12223), MSSA (ATCC 25923), MRSA (MU50), E. cloacae (ATCC 13047), and K. pneumoniae (ATCC 700603), compared to the control. The chemical profiles of crude extracts, both treated and untreated, were analyzed using gas chromatography–mass spectrometry and ultra-high-performance liquid chromatography along with high-resolution mass spectrometry). The results highlighted the capacity of UNC1999 to modulate the synthesis of cryptic metabolites in X. papulis, displaying antimicrobial and anticancer potential. This study underlines the importance of further research into the molecular mechanisms regulating these epigenetically modulated metabolic pathways.

Untargeted metabolomics and in silico analysis identifies potential DNA gyrase inhibitors from an endophytic fungus Alternaria alternata P02PL2

The escalating threat of multidrug-resistant (MDR) bacterial pathogens underscores the urgent need for novel antimicrobial agents. Here, we combined a one-strain many compounds (OSMAC) and untargeted metabolomics approaches to investigate the bioactivities and the chemical space of the endophytic fungus Alternaria alternata P02PL2, isolated from a medicinal plant, Sclerocarya birrea . The antibacterial activities were assessed against contemporary clinical isolates, MDR Pseudomonas aeruginosa 5625574, methicillin-resistant Staphylococcus aureus (MRSA) 5627679, and a collection culture of S. aureus ATCC 25923 for reference. We first tested for bioactivities across eight growth media to optimize the production of bioactive secondary metabolites. The bioactive fungal extract fractions exhibited minimum inhibitory concentrations (MICs) ranging from 0.25 to 0.5 mg/mL. This was followed by an untargeted metabolomics analysis, which identified 41 secondary metabolites. Virtual screening, molecular docking, and 200-ns molecular dynamics simulations targeting S. aureus and P. aeruginosa DNA gyrase revealed lead compounds with superior binding affinities (e.g., fluorescein −9.2 kcal/mol for P. aeruginosa ; pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro −8.8 kcal/mol for S. aureus ) compared to reference ligands. Binding free energy calculations highlighted strong affinities, with 5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-bis(3,4,5-trihydroxyoxan-2-yl)chromen-4-one (−42.16 kcal/mol) and fluorescein (−41.42 kcal/mol) outperforming the P. aeruginosa reference ligand evo (−19.80 kcal/mol) and 80s (−48.74 kcal/mol) leading for S. aureus . Per-residue energy decomposition and quantum chemical analyses further elucidated key interactions and reactivity profiles. These results position A. alternata P02PL2 as a promising source of DNA gyrase inhibitors to combat antimicrobial resistance. •  A. alternata extracts inhibits S. aureus and Pseudomonas with MIC of 0.25-0.5 mg/mL •  Inhibitors included Diketopiperazine (S. aureus), C-glycosyl flavone (Pseudomonas) •  In silico analyses suggest the metabolites putatively inhibit bacterial DNA gyrase

Integrated chemical and genomic analysis of lipopeptides produced by Bacillus velezensis CMRP4489 with antifungal activity

The present study is the first to report the antifungal activity of bacillopeptins against Sclerotinia sclerotiorum, a fungus responsible for white mold.

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

Overall, this study identifies P. lactis PEL6 as a promising endophytic source of anti-S.

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