Metabolomics Approach to Explore Bioactive Natural Products Derived From Plant-Root-Associated Streptomyces

Abstract

Streptomyces, a prominent genus within the Actinobacteria phylum, is responsible for over 60% of clinically relevant antibiotics. Streptomyces strains inhabiting plant roots possess the potential to synthesize bioactive natural products, conferring defense and resilience to plants against pathogenic microorganisms. However, this potential remains largely unexplored. This study aims to screen for bioactive metabolites produced by Streptomyces strains in the plant rhizosphere.Six Streptomyces isolates were cultivated using three modi ed media to induce the production of diverse metabolites, employing the OSMAC (One Strain Many Compounds) approach. Metabolite pro les of extracts from fermentation broths were analyzed using a non-targeted LC-MS/MS approach combined with GNPS molecular networking. The antimicrobial activity of the extracts was assessed using the disc diffusion method.The strains exhibited a broad-spectrum antimicrobial activity against all tested organisms, with particularly pronounced inhibition observed against Gram-positive bacteria and Candida albicans, resulting in inhibition zones exceeding 30 mm. Within the metabolomes of these strains, the antibiotics spiramycin and actinomycin were detected. Additionally, lyngbatoxin, a tumor promoter, and potential new analogs were identi ed. Notably, a substantial portion of the generated metabolites did not match any known compounds, implying the presence of unidenti ed metabolites produced by these strains, which could potentially introduce novel chemical entities.This study illuminates the potential for discovering bioactive compounds from Streptomyces strains associated with plant roots, offering valuable insights for antimicrobial drug development. Furthermore, the metabolomics approach utilized in this study serves as a rapid and valuable tool for the screening of microorganisms capable of producing bioactive metabolites.