Combating Fusarium Wilt: A Metabologenomics Approach Identifies Stendomycins as Promising Sustainable Biocontrol Agents.

The phytopathogen Fusarium oxysporum threatens global food security, necessitating sustainable biocontrol alternatives to chemical fungicides. Here, we employed an OSMAC-driven dual-layer fast screening (DLFS) approach to identify Streptomyces sp. OUC-HL1638 as a potent antagonist. Through integrated NMR-based lipopeptide signature mapping and LC-MS-assisted NRPS gene mining, we efficiently targeted and isolated two stendomycins (1 and 2). These compounds exhibited potent in vitro antifungal activity (MIC = 1 μM), outperforming hymexazol by 1000-fold, and effectively controlled F. oxysporum infection in radish seedlings and postharvest cherry tomatoes without phytotoxicity. The producing strain intrinsically balances stendomycin production with low plant toxicity and sustains production under high-salinity and alkaline conditions, indicating potential for saline-alkaline agriculture. This work establishes an efficient pipeline for green fungicide discovery and highlights the promise of stendomycins and strain OUC-HL1638 as sustainable biocontrol agents for crop protection.