Secondary Metabolite Biosynthesis Potential of <i>Streptomyces</i> Spp. from the Rhizosphere of <i>Leontopodium nivale</i> Subsp. <i>alpinum</i>

Bacteria of the phylum Actinomycetota, particularly those of the genus <i>Streptomyces</i>, are prolific producers of secondary metabolites (SMs), many of which have been developed into antibiotics, immunosuppressants, and cancer therapeutics. With high rediscovery rates, the attention has shifted to <i>Streptomyces</i> from unique ecological niches for the discovery of new SMs. The plant rhizosphere is one such niche, characterized by complex chemical interactions between the plant and its rhizobiome, which can elicit the production of SMs in <i>Streptomyces</i>. In the present study, 18 S<i>treptomyces</i> strains were previously isolated from the rhizosphere of the rare alpine medicinal plant <i>Leontopodium nivale</i> subsp. <i>alpinum</i> were investigated for their capacity to produce secondary metabolites. Genomes of these strains were analyzed for the presence of SM biosynthetic gene clusters (BGCs). In total, 551 BGCs were detected, of which 217 could not be linked to known SMs. These isolates were cultivated in different media known to support the production of SMs, and 15 out of the 54 methanolic extracts from these cultures exhibited antimicrobial activities. Subsequent liquid chromatography-mass spectrometry analyses of the bioactive extracts led to a putative identification of 69 known SMs as well as 16 potentially new molecules. The results of this study may provide a basis for the discovery of unique molecules with the potential to be developed as drugs against a variety of human diseases.