Integrative Genomic and Experimental Characterization of Silent Biosynthetic Gene Clusters in Rare Environmental Microorganisms for Anticancer Metabolite Discovery

Abstract

Genomic and experimental investigation of anticancer metabolites of rare environmental microorganisms were performed in the current research. In total, 109 gene clusters, namely NRPS, PKS, RiPP, terpene, and others, have been identified by the genome mining of four selected microorganisms. Five gene clusters characterized by low homology to other BGCs and specific genetic features have been chosen for experimental evaluation. Metabolite profiling performed during cultivation of microorganisms resulted in the identification of peptide-, polyketide-, and hybrid-type compounds with the mass values of 514.2–856.4 Da. In terms of anticancer activity, REM-01-M2 and REM-03-M1 metabolites have shown the best results, providing 64.2% and 60.3% growth inhibition in MCF-7 cells, respectively. Overall, rare environmental microorganisms proved to be promising sources of biosynthesis diversity, while the combination of genome mining, experimental evaluation, and biological screening was proved to be an efficient approach for the identification of anticancer metabolites of microbes. Further investigations are needed to determine the chemical structures and safety of the compounds in question.