D-Carvone Inhibits Fusarium oxysporum by Modulating Gene Expression Through Reduced Histone 3 Acetylation.

Fusarium oxysporum is a significant soilborne pathogen affecting global agriculture, causing root rot in crops, such as Panax notoginseng. Environmentally friendly pesticides are required to control this threat. We examined the antifungal effects of D-carvone on F. oxysporum using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq). D-carvone significantly inhibited F. oxysporum growth at a median effective concentration of 2.218 mM, reducing spore germination, viability, production, and hyphal dry weight by 53.89, 66.65, 64.71, and 40.95%, respectively. RNA-seq identified 3,812 differentially expressed genes: 1,044 upregulated and 2,768 downregulated, primarily affecting ribosome biogenesis and spliceosome pathways. H3K9ac and H3K27ac levels significantly decreased after D-carvone treatment, and several histone acetyltransferase (HAT) genes, including FOBCDRAFT_229079 (FoADA2), FOBCDRAFT_252088 (FoRTT109), FOBCDRAFT_264101 (FoSAS2), and FOBCDRAFT_255231, were downregulated. D-carvone showed strong binding affinity to HATs, suggesting that it inhibits F. oxysporum growth by reducing HAT expression and activity and lowering H3K9ac and H3K27ac modifications. Integrating ChIP-seq with RNA-seq indicated that H3K9ac downregulation is linked to spliceosome activity, transcriptional regulation, ribosome biogenesis, and mismatch repair. D-carvone reduced H3K9ac and H3K27ac levels, decreasing the expression of spliceosome-related genes (FOBCDRAFT_4119, FOBCDRAFT_210951, and FOBCDRAFT_229024) and ribosome biogenesis genes (FOBCDRAFT_210393, FOBCDRAFT_224097, and FOBCDRAFT_173414). This study provides new insights into developing strategies to combat fungal pathogens.