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Peer-reviewedCC BY 4.0Frontiers in Microbiology

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

  1. 1Chemical and Pharmaceutical Biology, University of Groningen
  2. 2University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, University of Groningen
  3. 3European Institute of Innovation and Technology (EIT), Healthy Ageing PhD School, University Medical Center Groningen, University of Groningen

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.

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BibTeX
@article{li2026genomics,
  title = {{Genomics and metabolomics analyses reveal the endophytic fungus Neocucurbitaria sp. VM-36 as a potential source of bioactive metabolites against methicillin-resistant Staphylococcus aureus}},
  author = {Xiao Li and Rosario del Carmen Flores-Vallejo and Ting He and Jan Maarten van Dijl and Kristina Haslinger},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1929829},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1929829/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Genomics and metabolomics analyses reveal the endophytic fungus Neocucurbitaria sp. VM-36 as a potential source of bioactive metabolites against methicillin-resistant Staphylococcus aureus
AU  - Xiao Li
AU  - Rosario del Carmen Flores-Vallejo
AU  - Ting He
AU  - Jan Maarten van Dijl
AU  - Kristina Haslinger
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1929829
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1929829/full
AB  - 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.
SN  - 1664-302X
ER  -