Naringenin Inhibits the Growth of Diaporthe citri by Targeting Fungal Glucokinase

Diaporthe citri, a pathogenic fungus affecting citrus, has developed resistance to chemical fungicides. Developing botanical fungicides is crucial for effectively controlling this pathogen. In this study, we found naringenin, a natural flavonoid, has inhibitory activity against D. citri. Target screening identified D. citri glucokinase (DcGCK), a key enzyme in glucose metabolism, as a novel target of naringenin. Further binding analysis confirmed the high-affinity binding between DcGCK and naringenin. Specifically, naringenin competitively binds to the active pocket of DcGCK, disrupting binding of glucose to DcGCK and thereby inhibiting its activity. Deletion of DcGCK significantly suppressed D. citri growth and pathogenicity. Moreover, transcriptome and metabolite analyses demonstrated that naringenin disrupts sugar metabolism in D. citri. Our results elucidate that naringenin directly targets DcGCK and interferes with fungal sugar metabolism. This reveals a novel mechanism by which naringenin inhibits pathogenic fungal growth and provides a new strategy to protect plants from D. citri.