Identification of the biosynthetic gene cluster for desmethylmensacarcin, a phytotoxic polyketide produced by Streptomyces niveiscabiei ST1015

This work reports the first functional characterization of the biosynthetic gene cluster (BGC) responsible for the production of the phytotoxic polyketide desmethylmensacarcin (dmsn) in Streptomyces niveiscabiei ST1015, a potato common scab pathogen. Using genome sequencing and comparative analysis, a 22-gene type II polyketide synthase (PKS) cluster was discovered with high identity to the mensacarcin (msn) cluster from Streptomyces bottropensis but lacking the three methyltransferase genes (msnM1–M3), confirming dmsn as the final product. Dmsn production was detected only in plant-based media and correlated with phytotoxic activity in radish seedling and potato tuber assays. Quantitative analysis based on seedling length ratios relative to the water control showed a ∼90 % reduction in the phytotoxic effect of culture supernatants from the mutants lacking the core ketosynthase genes ( dmsnK1–K2 ) compared to the wild type ( p < 0.001). Genetic complementation of the mutants restored the phytotoxicity to wild-type levels. Surprisingly, the mutant strains remained virulent on potato, suggesting that dmsn is not the sole determinant of pathogenicity in ST1015. BiG-SCAPE analysis revealed that msn/dmsn-like BGCs are more widely distributed among pathogenic Streptomyces species than previously recognized, although some strains carry non-functional clusters due to premature stop codons or possible regulatory divergence. These findings suggest that multiple potentially redundant phytotoxic pathways may contribute to common scab pathogenesis. This work highlights the widespread occurrence and functional diversity of dmsn-like clusters and provides new insights into the ecological and genetic complexity underlaying common scab pathogenesis. • Desmethylmensacarsin (dmsn) contributes to tissue damage in potato common scab. • Dmsn production is restricted to plant-based media and correlates with phytotoxicity. • The biosynthetic gene cluster (BGC) for dmsn was identified in Streptomyces niveiscabiei ST1015. • Deletion of dmsnK1–K2 abolishes dmsn synthesis and supernatant toxicity. • Dmsn BGC is also present in other S. niveiscabiei and S. acidiscabies genomes.