Natural Products Targeting the Fungal Unfolded Protein Response as an Alternative Crop Protection Strategy

Area of Science:

• Plant Pathology
• Mycology
• Biochemistry

Background:

• Crop protection faces challenges from fungicide resistance, climate change, and ecotoxicity.
• Targeting the fungal unfolded protein response (UPR) is a promising strategy for plant disease control.
• The UPR pathway influences fungal virulence and susceptibility to plant defense compounds.

Purpose of the Study:

• To identify natural products that inhibit the fungal IRE1 protein, a key effector in the UPR pathway.
• To evaluate the efficacy of these compounds in increasing fungal susceptibility to plant defenses.
• To investigate the interaction between inhibitors and the IRE1 binding site.

Main Methods:

• Development of an in vitro cell-based screening assay for IRE1 inhibitors.
• Identification and characterization of potential inhibitors, focusing on polyhydroxylated prenylated xanthones.
• Validation of IRE1 inhibition via HAC1 mRNA splicing assays and molecular docking studies.
• Assessment of the impact of active compounds on plant disease symptoms in Brassica oleracea.

Main Results:

• Seven potential IRE1 inhibitors were identified, with a focus on xanthones.
• The compound γ-mangostin demonstrated significant inhibition of HAC1 mRNA splicing.
• Molecular docking revealed detailed interactions between xanthones and the IRE1 binding site.
• Subtoxic doses of active xanthones reduced necrosis in Brassica oleracea leaves infected with Alternaria brassicicola and Botrytis cinerea.

Conclusions:

• Polyhydroxylated prenylated xanthones are effective inhibitors of the fungal IRE1 protein.
• Targeting the UPR pathway with natural products offers a novel strategy for crop protection.
• These findings provide a basis for developing new, eco-friendly fungicides.