Anticancer compounds from Streptomyces: insights from metagenomics and mechanistic perspective

Cancer continues to be a leading cause of death globally, driving the ongoing search for novel bioactive compounds with therapeutic potential. Metagenomic sequencing has revolutionized this pursuit by enabling the direct detection and genomic assembly of previously uncultured Streptomyces species from environmental DNA, circumventing traditional cultivation limitations. This review explores recent advances in metagenomics-driven discovery of anticancer compounds derived from Streptomyces, with a focus on identifying biosynthetic gene clusters (BGCs) responsible for producing bioactive secondary metabolites. Over the past decade, metagenomic approaches have been adopted to uncover new species of Streptomyces and anticancer compounds. Although metagenomics has been adopted in research and discovery of new Streptomyces, its application in the discovery of Streptomyces-related pathways pertaining to anticancer compounds remains limited. Furthermore, clinical translation remains limited, highlighting the need for further research. By examining metagenomic methodologies and the mechanisms of action of these compounds, this review provides an updated and focused perspective on Streptomyces-derived anticancer agents and their potential for future drug development.