Unlocking antifungal mechanisms of natural 3-(oxazole-5-yl) indole compound derived from Streptomyces syringium against plant gray mold caused by Botrytis cinerea.

BACKGROUND: Plant fungal diseases cause significant agricultural losses, and Streptomyces-derived antifungal compounds offer a promising biocontrol strategy. This study aimed to isolate and characterize bioactive metabolites from Streptomyces syringium LZ036 and evaluate their activity and mechanism of action against Botrytis cinerea. RESULTS: A strain LZ036 with broad-spectrum antifungal activity was identified as Streptomyces syringium. The 3-(oxazole-5-yl) indole compound NL3 isolated from this strain exhibited potent broad-spectrum antifungal activity, especially against Botrytis cinerea. Compound NL3 inhibited fungal growth and development by inducing severe oxidative damage and membrane disruption. And it could trigger jasmonic acid (JA)-dependent induced systemic resistance (ISR) in plants. Transcriptomic analysis of compound NL3-treated Botrytis cinerea revealed genome-wide transcriptional alterations, including disruption of energy metabolism and mitochondrial function. Key genes related to mitogen-activated protein kinase (MAPK) signaling pathway down-regulated significantly, among which the catalytic S_TKc domain of Bcste7 exhibited a predicted interaction with compound NL3 through hydrophobic interactions and hydrogen bonding. CONCLUSION: The Streptomyces syringium-derived compound NL3 shows high potential as a green fungicide, acting through multiple mechanisms. These findings advance the development of Streptomyces-based antifungal agents. © 2026 Society of Chemical Industry.