The natural polycyclic tetramate macrolactam HSAF inhibit Fusarium graminearum through altering cell membrane

Wenchan Chen1, Bao Tang1, Rongxian Hou1

  • 1Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210095, Jiangsu, China.

Insights

Heat-stable antifungal factor (HSAF) targets the FgORP1 protein in Fusarium graminearum, reducing fungal virulence and DON production. This discovery offers a promising new fungicide strategy for controlling Fusarium head blight in cereals.

Area of Science:

  • Agricultural Science
  • Mycology
  • Biochemistry

Background:

  • Fusarium graminearum causes Fusarium head blight (FHB), a major threat to cereal crops.
  • Heat-stable antifungal factor (HSAF) shows potent antifungal activity against F. graminearum, reducing mycotoxin production and virulence.
  • The specific molecular target of HSAF in F. graminearum remained unidentified.

Purpose of the Study:

  • To identify the target protein of HSAF in F. graminearum.
  • To elucidate the mode of action of HSAF against F. graminearum.
  • To evaluate HSAF as a potential fungicide for FHB control.

Main Methods:

  • Surface plasmon resonance (SPR) and RNA-sequencing (RNA-seq) were employed to identify HSAF's target.
  • Molecular docking was used to predict binding sites of HSAF on the target protein.
  • Site-directed mutagenesis and gene deletion were performed to validate the target and its role.

Main Results:

  • The oxysterol-binding protein FgORP1 was identified as the direct target of HSAF.
  • HSAF interacts with arginine 1205 and glutamic acid 1212 within the oxysterol-binding domain of FgORP1.
  • FgORP1 plays a crucial role in regulating fungal growth, development, mycotoxin production, and virulence.

Conclusions:

  • FgORP1 is the molecular target of HSAF, mediating its antifungal effects.
  • HSAF disrupts ergosterol biosynthesis and cell membrane integrity in F. graminearum.
  • HSAF represents a novel and promising fungicide candidate for managing FHB.

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