Genomics and metabolomics analyses reveal the endophytic fungus Neocucurbitaria sp. VM-36 as a potential source of bioactive metabolites against methicillin-resistant Staphylococcus aureus

Abstract

Endophytic fungi associated with medicinal plants represent valuable sources of specialized metabolites with potential biological activities. Here, we investigated Neocucurbitaria sp. VM-36, an understudied endophyte isolated from the medicinal plant Vinca minor , using an integrated genomic, metabolomic, and antibacterial approach. Whole genome analysis suggests substantial biosynthetic potential for a range of secondary metabolites based on the presence of various biosynthetic gene clusters. Metabolomic profiling revealed a broad chemical repertoire, including metabolites putatively assigned as decalin-containing tetramic acids (DTAs). Among the compounds examined experimentally, compound 1 was structurally identified and exhibited potent antibacterial activity against Gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), with MIC and MBC values of 0.5–1 and 2–4 μg/mL, respectively. Compound 1 displayed rapid bactericidal activity and showed an additive effect in combination with daptomycin against a clinical MRSA isolate (FICI = 0.625). These findings provide evidence for the occurrence of DTA-related metabolites in Neocucurbitaria and experimentally demonstrate the antibacterial activity of compound 1 . Collectively, this study provides integrated genomic and metabolomic insights into an endophytic Neocucurbitaria strain, expands the known occurrence of DTA-related metabolites in fungi, and supports the potential of Neocucurbitaria as a source of antibacterial hit compounds.