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

Introduction Endophytic fungi associated with medicinal plants represent valuable sources of specialized metabolites with potential biological activities. Methods 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. Results 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. Discussion 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.