Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity

Abstract

SummaryAs phospholipids of cell membranes, phosphatidylethanolamine (PE) and phosphatidylserine (PS) play crucial roles in glycerophospholipid metabolism. Broadly, some phospholipid biosynthesis enzymes serve as potential fungicide targets. Therefore, revealing the functions and mechanism of PE biosynthesis in plant pathogens would provide potential targets for crop disease control.We performed analyses including phenotypic characterizations, lipidomics, enzyme activity, site-directed mutagenesis, and chemical inhibition assays to study the function of PS decarboxylase-encoding geneMoPSD2in rice blast fungusMagnaporthe oryzae.TheMopsd2mutant was defective in development, lipid metabolism and plant infection. The PS level increased while PE decreased inMopsd2, consistent with the enzyme activity. Furthermore, chemical doxorubicin inhibited the enzyme activity of MoPsd2 and showed antifungal activity against ten phytopathogenic fungi includingM. oryzaeand reduced disease severity of two crop diseases in the field. Three predicted doxorubicin-interacting residues are important for MoPsd2 functions.Our study demonstrates that MoPsd2 is involved inde novoPE biosynthesis and contributes to the development and plant infection ofM. oryzaeand that doxorubicin shows broad-spectrum antifungal activity as a fungicide candidate. The study also implicates that bacteriumStreptomyces peucetius, which biosynthesizes doxorubicin, could be potentially used as an eco-friendly biocontrol agent.