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This research aims to identify antifungal natural products from fungal metabolites to combat plant phytopathogenic fungi.

March 10, 2026

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Bioactivity‐guided discovery of two novel hybrid polyketides with antifungal activity against phytopathogens

LSLiyue SuHebei University MRMeng RenHebei Agricultural University JWJintao WangHebei University

Key Points

This research aims to identify antifungal natural products from fungal metabolites to combat plant phytopathogenic fungi.
Bioactivity-guided isolation of natural products from Aspergillus novofumigatus.
Characterization of antifungal effects using EC50 values against multiple phytopathogens.
Microscopy techniques to examine cell membrane damage after treatment with novomycin B.
Transcriptomic analysis to assess impacts on DNA replication and energy metabolism.
Novomycin B shows broad-spectrum antifungal activity, with EC50 ranging from 0.84 to 53.32 μg mL−1.
Complete inhibition of Botryosphaeria dothidea at 50 μg mL−1, surpassing the efficacy of Hymexazol.
Significant cell membrane damage as evidenced by microscopy and increased electrical conductivity and malondialdehyde levels.
Inhibition of antioxidant enzymes leading to increased hydrogen peroxide accumulation.
Impact on DNA replication and energy metabolism confirmed through transcriptomic analysis and ATP measurements.

Abstract

Abstract BACKGROUND Plant phytopathogenic fungi (PF) pose a significant threat to global agriculture by reducing crop yields and quality. The excessive use of chemical synthetic fungicides has raised concerns about environmental pollution and human health risks, while simultaneously accelerating the emergence of pathogen resistance. In this study, we aimed to discover antifungal natural products (NPs) from fungal metabolites, which represent promising eco‐friendly alternatives, via bioactivity‐guided isolation. RESULTS Two novel hybrid polyketides, novomycins A and B, were isolated from Aspergillus novofumigatus J2‐22. Novomycin B demonstrated broad‐spectrum antifungal activity against eight PF strains, with half‐maximal effective concentration (EC 50 ) values ranging from 0.84 to 53.32 μg mL −1 . Notably, novomycin B exhibited superior antifungal activity compared to the agricultural fungicide Hymexazol, achieving 100% inhibition of Botryosphaeria dothidea at 50 μg mL −1 . Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed that novomycin B treatment caused severe destruction to the cell membrane, as evidenced by measurements of electrical conductivity, soluble protein content, and ergosterol content. Besides, novomycin B inhibited the activities of antioxidant enzymes (superoxide dismutase and catalase) in B . dothidea , leading to accumulation of hydrogen peroxide and malondialdehyde, which further exacerbated membrane system damage. Transcriptomic data indicated that novomycin B severely impaired DNA replication systems and activated extensive DNA damage repair mechanisms, which was further supported by TUNEL and EdU incorporation assays. Furthermore, it impaired energy metabolism, as confirmed by the inhibition of ATPase activity and decreased adenosine triphosphate (ATP) content. CONCLUSION These results demonstrate that novomycin B, as a natural fungicide exhibiting multi‐target antifungal mechanisms, provides a theoretical foundation for its development as an agricultural fungicide. © 2026 Society of Chemical Industry.

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Bioactivity‐guided discovery of two novel hybrid polyketides with antifungal activity against phytopathogens

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