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 (fourth instar), comparable to the bioinsecticide spinetoram (Radiant SC 12%). Endophytes from Artemisia herba-alba and A. judaica were highly effective. Chemical profiling of the most potent metabolite of the strain Streptomyces sp. ES2 was investigated using LC-QTOF-MS-MS technique, and the activity was validated through molecular docking studies. Metabolic extracts from actinobacteria belonging to Streptomyces, Nocardioides, and Pseudonocardia showed immediate and latent death to the Spodoptera littoralis fourth instar larvae. The metabolite from strain ES2 has shown the most promising and significant histopathological and inhibitory effects on the fourth instar larvae. ES2 metabolite caused lesions in the body wall cuticle, indicating a different mode of action than that of Radiant. Chemical profiling of ES2 showed the 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 can be a sustainable source for promising natural biocontrol agents. This is the first illustration of the insecticidal activity of Artemisia spp. microbiome, and natural cyromazine synthesis by actinobacteria.

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.