Pyrrocidines A and B demonstrate synergistic inhibition of growth.

-a mycotoxigenic fungus and food safety threat-coinhabits maize kernels with . This protective endophyte produces secondary metabolites of interest, pyrrocidines A and B, which inhibit the growth of and specifically block fumonisin biosynthesis. Previous transcriptomic analyses found (FVEG_00314), a gene adjacent to the fumonisin biosynthetic gene cluster, to be induced over 4,000-fold in response to pyrrocidine challenge. Deletion of resulted in dramatic increases in fumonisin production (FB >30-fold). Here, using pyrrocidine dose-response assays, we discovered a potent synergy between pyrrocidines A and B, where they functioned powerfully together to inhibit growth. Further, results provided evidence that confers partial tolerance to pyrrocidines, particularly pyrrocidine A, and that pyrrocidine functions through to effectively eliminate fumonisin biosynthesis. Additionally, we showed that the (FVEG_11089) mutant, earlier described as hypersensitive to pyrrocidine, is particularly sensitive to pyrrocidine B. Thus, pyrrocidine A and B show different target specificity ( or ) and synergistic action. These findings will help inform the optimization of maximally efficacious strains for eliminating colonization and fumonisin contamination in maize cropping systems. This novel study contributes significantly to our knowledge of competitive microorganism relationships and the role of secondary metabolites in antagonistic fungal-fungal interactions.