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

Banana wilt, caused by f. sp. , threatens global banana production. Biocontrol using is a promising strategy. Here, we identified D337-11 from disease suppressive banana soils, which exhibited dual functionality in controlling f. sp. tropical race 4 ( 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 TR4, particularly, reviving 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 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 -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.