Artemisia-derived Actinobacteria Producing Inhibitors of Spodoptera Littoralis via Molecular Modeling Studies

Abstract Insecticide resistance in agricultural pests has prompted the need to discover novel compounds with new modes of action. We investigated the potency of secondary metabolites from seventy endophytic actinobacteria against laboratory and field strains of Spodoptera littoralis (4th instar), comparable to spinetoram (Radiant® 12% SC). Endophytes from Artemisia herba-alba (syn. Seriphidium herba-alba) and Artemisia judaica were highly effective. Chemical profiling of the most potent metabolite was investigated using LC-QTOF-MS-MS technique, and the activity was validated through molecular docking studies. Metabolic extracts from seven actinobacteria (belonging to Streptomyces, Nocardioides, Kitasatospora and Pseudonocardia) have shown lethality to the 4th instar larvae. The metabolite ES2, from Kitasatospora sp., caused significant histopathological and inhibitory effects on 4th instar larvae. Additionally, ES2 caused lesions in the body wall cuticle, indicating a different mode of action than that of spinetoram. Chemical profiling of ES2 have shown presence of cyromazine (molt inhibitor), 4-nitrophenol and diazinon as key constituents. In conclusion, these findings suggest that, secondary metabolites from endophytic actinobacteria inhabiting wild medicinal plants are sustainable source for promising natural biocontrol agents. This is the first illustration of insecticidal activity of the Artemisia spp. microbiome, and the first report on a natural cyromazine synthesized by actinobacteria.