Genome-guided investigation of secondary metabolites produced by a potential new strain Streptomyces BA2 isolated from an endemic plant rhizosphere in Turkey.

Terrestrial actinomycetes are the important sources of secondary metabolites that serve as a major source of drugs. Recent advances in genome mining have revealed that Streptomyces genomes have a wide range of undiscovered secondary metabolite biosynthetic gene clusters. In the present study, genome mining was employed to discover biosynthetic potential of plant-associated strain Streptomyces BA2. Based on 16S rRNA gene sequencing, this strain was found to be closely related to Streptomyces durmitorensis, Streptomyces alboniger, and Streptomyces kanamyceticus with similarity of 99.71%, 99.64%, and 99.56%, respectively. The genome of BA2 contained 10.043.478 base pairs with G + C content of 69.92%. The annotation results revealed the presence of 9.056 protein coding genes, 88 tRNA and 18 rRNA genes. The dDDH and ANI values of genome sequences between strain BA2 and closely related type strains were considerably lower than the recommended threshold values. A total of 33 secondary metabolite biosynthetic gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including non-ribosomal peptides, polyketides, terpenes, siderophores, bacteriocins, ectoines, and lassopeptides were identified. Metabolic profiling of Streptomyces sp. BA2 grown in three different culture media was determined by a non-targeted LC-MS/MS approach coupled with spectral networking. Significant bioactive natural products such as actinomycin D, desferrioxamine E, malyngamide K, and bouillonamide B were detected. Malyngamide K and bouillonamide B, known as marine cyanobacterial-derived compounds, were first reported from a Streptomyces strain in this study. Our study demonstrated the potentially novel strain Streptomyces sp. BA2 as a valuable source of new bioactive secondary metabolites.

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

Streptomyces, a prominent genus within the Actinomycetota 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 modified media to induce the production of diverse metabolites, employing the One Strain Many Compounds (OSMAC) approach. The metabolites present in extracts from fermentation broths were examined through a non-targeted Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach coupled with Global Natural Products Social Molecular Networking (GNPS MN). The antimicrobial activity of the extracts was assessed using the disc diffusion method.The strains demonstrated a wide-ranging antimicrobial efficacy against all examined organisms. The GNPS molecular network analyses reveal that metabolite profiles in extracts can exhibit variations based on the medium and solvent system employed. Notably, the ethyl acetate and dichloromethane extracts from Streptomyces sp. CAH29, cultivated in Glucose-Yeast Extract Medium (GYM), exhibited inhibition diameters of up to 30 mm against both Staphylococcus aureus and Candida albicans. Within the metabolomes of these strains, the antibiotics spiramycin and actinomycin were detected. Additionally, lyngbatoxin, a tumor promoter, and potential new analogs were identified. Significantly, a considerable portion of the produced metabolites did not align with any known compounds, indicating the existence of unidentified metabolites generated by these strains. This suggests the possibility of introducing novel chemical entities.Our study illustrated that Streptomyces strains associated with plant roots could be considered a valuable source of bioactive secondary metabolites. 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.