Biocontrol potential of newly isolated Streptomyces noursei D337-11 from disease suppressive soil and its metabolites against Fusarium oxysporum f. sp. cubense in banana plants

Banana <i>Fusarium</i> wilt, caused by <i>Fusarium oxysporum</i> f. sp. <i>cubense</i>, threatens global banana production. Biocontrol using <i>Streptomyces</i> is a promising strategy. Here, we identified <i>Streptomyces noursei</i> D337-11 from disease suppressive banana soils, which exhibited dual functionality in controlling <i>F. oxysporum</i> f. sp. <i>cubense</i> tropical race 4 (<i>Foc</i> TR4), achieving a 65.35% suppression of disease, and promoting plant growth in pot experiments. The extracts from this strain restored the soil microbiota disrupted by <i>Foc</i> TR4, particularly, reviving <i>Saccharimonadales</i> populations. Using integrated untargeted metabolomics (LC-ESIMS/MS) and genomic analysis, we identified five bioactive metabolites, including naringenin, a flavonoid linked to a 100% homologous biosynthetic gene cluster (Region 52.1). Genome-guided differential metabolomics established the genetic basis for flavonoid production. Mechanistic characterization indicated that naringenin exhibits antifungal activity via dual-target inhibition: molecular docking showed strong binding to the trypsin of <i>Foc</i> TR4 (N1RZA7, -6.6 kcal/mol) and nitroalkane oxidase (N1R9V2, -8.4 kcal/mol), which disrupts cellular integrity as evidenced by ultrastructural anomalies. We provide the first evidence of <i>Streptomyces</i>-derived naringenin as a multi-target antifungal agent. Overall, this study provides a theoretical basis for exploring the application of microbial flavonoids in biological control of fungal diseases.