New Marine Actinobacteria Strain, Micromonospora sp. SH-82: Characterization, Specialized Metabolites and Biological Activities

The study of various microorganisms isolated from an Indian Ocean sponge, <i>Scopalina hapalia</i> ML-263, led to the selection of a promising Actinobacteria strain, <i>Micromonospora</i> sp. SH-82. Genomic analysis identified this strain as a new species, revealing the presence of 23 biosynthetic gene clusters (BGCs), some of which are associated with the synthesis of specialized metabolites such as polyketides deriving from polyketide synthases (PKSs). The strain was cultivated under favorable conditions for the production of bioactive molecules, resulting in the isolation and identification of seven microbial metabolites. Three of them are potentially novel, two erythronolides and one erythromycin, all characterized by a rare C10-C11 double bond. Some of these compounds also display atypical conformations, forming hemiacetals or spiroacetals. Their identification was achieved through detailed chemical analyses (NMR and ESI⁺-HRMS). A molecular networking approach was employed to assess the presence of potentially novel molecules in the microbial crude extract, supported by the identification of isolated molecules. Four molecules (<b>1</b>, <b>2</b>, <b>3</b> and <b>5</b>) were evaluated for their cytotoxic activities against cancer cell lines (HCT-116 and MDA-MB-231) and the immortalized retinal pigment epithelial RPE1 cells. No activity was observed in the latter, suggesting a lack of toxicity toward healthy cells. Moreover, megalomicin C1 (3), one of the isolated compounds, showed interesting antiplasmodial activity against <i>Plasmodium falciparum</i> 3D7, with an IC₅₀ of 6.37 ± 2.99 µM.