Genome mining of secondary metabolites from Streptomyces spp. for the screening of novel and potent fungicide: Focus on rice blast disease

Rice stands as the most consumed commodity globally, serving as the primary energy source for nearly half of the world's population. However, rice blast disease, caused by the fungus Magnaporthe oryzae, leads to significant production losses. This research focuses on devising a sustainable solution against M. oryzae using advanced computational techniques including genome mining and in silico screening. The melanin pathway in M. oryzae involving the conversion of tyrosine to melanin is crucial for its pathogenicity. Succinate dehydrogenase (SDH) plays a key role in this pathway by catalysing the oxidation of succinate to fumarate, thereby contributing to the production of melanin. Currently, carpropamid is used as a commercial inhibitor for rice blast disease due to its broad-spectrum fungicidal activity. However, its unintended harm to non-target organisms presents limitations, highlighting the need for alternative solutions to combat rice blast disease. Streptomyces-derived bio-fungicides emerge as a promising alternative, harnessing bioactive chemicals produced by plant endophytic bacteria to suppress pathogen growth. The research leveraged genome mining from the 23 whole genome sequence of plant endophytic streptomyces. This process yielded 3343 putative molecules and further reduced to 906 compounds after removing duplicates. These compounds were subjected to a series of molecular simulation strategy to unveil the potent fungicide compound. Ultimately, the study identifies Cremeomycin and Azetidomonamide B as secondary metabolites with superior binding affinity, interaction and fungicidal potential compared to carpropamid. The future trajectory of this research entails experimental validation and the development of sustainable bio-fungicides against rice blast disease.