Phenazine-1-carboxylic Acid Has a Broad-Spectrum Antifungal Effect by Targeting Isocitrate Lyase

Phenazine-1-carboxylic acid (PCA), as a broad-spectrum antifungal agent, showed significant resistance against the Apple Valsa canker caused by <i>Valsa mali</i> (<i>V. mali</i>). Therefore, it is of great importance to reveal the functions and mechanisms of PCA in plant pathogens, which would provide potential targets for crop disease control. In this study, we identified the major contribution of PCA in the resistance of <i>Pseudomonas chlororaphis</i> subsp. <i>aureofaciens</i> W9-1 to <i>V. mali</i> by gene knockout and high-performance liquid chromatography. Subsequently, we demonstrated that PCA could target isocitrate lyase (ICL) to exert a broad-spectrum antifungal effect by molecular docking, microscale thermophoresis, and isothermal titration calorimetry. Furthermore, lipidomics analysis shows that PCA alters the lipid balance at the cell membrane of <i>V. mali</i>. In summary, this study demonstrates that PCA has a broad-spectrum antifungal effect by targeting the ICL, which may be a potential target for the development and utilization of fungicides.