New 24-Membered Macrolactins Isolated from Marine Bacteria Bacillus siamensis as Potent Fungal Inhibitors against Sugarcane Smut.

Sugarcane smut, caused by Sporisorium scitamineum, is one of the most devastating fungal diseases affecting sugarcane worldwide. To develop a potent sugarcane smut fungicide, secondary metabolites of marine-derived Bacillus siamensis were isolated and screened for inhibitory activities, which led to the discovery of five new 24-membered macrolactins, bamemacrolactins A-E (1-5), with 3 being the most potent inhibitor. The antifungal mechanism of 3 was studied by assessing its effects on mycelial morphology and the cell wall. Differential proteomics were used to analyze proteins in S. scitamineum upon treatment with bamemacrolactin C and to elucidate its antifungal mechanism. A total of 533 differentially expressed proteins were found. After the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, eight target proteins were selected, and their functions were discussed. Six of the eight proteins were reported as antifungal targets. The target proteins are involved in the oxidative phosphorylation pathway. Therefore, the potent inhibition of S. scitamineum by compound 3 is most likely through oxidative phosphorylation and targeting a series of enzymes.