Metabolomic and genomic insights into Micromonospora carbonacea subsp. caeruleus for anti-colorectal compound

Abstract

Cancer is a predominant contributor to global morbidity and mortality, affecting populations worldwide. Marine Micromonospora species have been identified as significant sources of anticancer compounds. This work aimed to perform a polyphasic approach of isolated strain and conduct comparative metabolomic and genomic analyses to identify compounds with anticancer activity. The study utilized a polyphasic approach on isolated strains for anticancer compound identification. Taxonomic analysis of strain 2MTK254 revealed unique pigment and fatty acid patterns, designating it as a novel Micromonospora carbonacea subsp. caeruleus. Its crude extract displayed significant anti-colorectal activity (66.03% inhibition). Molecular network analysis classified metabolites into eight classes, highlighting a polycyclic tetramate macrolactams (PTMs) compound (P1, C29H38N2O4) with 99.31% inhibitory activity against HCT-116 cell lines (IC50 at 0.125 µM). Genome analysis identified 32 biosynthetic gene clusters (BGCs), including unique PTMs BGCs (83% similarity) linked to the P1 compound. Thus, M. carbonacea subsp. caeruleus 2MTK254 holds promise as a source of novel PTMs with anti-colorectal cancer potential. KEY POINTS: • A novel strain of Micromonospora carbonacea subsp. caeruleus 2MTK254 was isolated in Thailand • A new polycyclic tetramate macrolactam (PTM) with anticancer activity was identified in 2MTK254 • The genome of 2MTK254 has unique secondary metabolite gene clusters.