Microprotein-based resistance to fusarium trichothecenes for crop protection

Overview

Fusarium graminearum is a devastating fungal pathogen that produces trichothecenes, potent mycotoxins that contaminate grain crops and threaten food security. This research explores a novel defense mechanism based on microproteins—small proteins encoded by short open reading frames that are often overlooked in traditional genomic analyses. The team has identified a microprotein from yeast that confers full resistance to more than double the lethal dose of the type B trichothecene trichothecin, without altering cell membrane permeability. The central hypothesis is that plants produce analogous microproteins that participate in the fungal-plant interaction, opening a new avenue for engineering durable resistance to Fusarium and reducing mycotoxin contamination in cereals.

Technical specifications

• Discovery platform: High-throughput screen of a yeast ORF overexpression library to identify genes that confer trichothecene resistance when overexpressed.
• Lead asset: A novel microprotein providing full resistance at 2.5X the lethal dose of trichothecin, confirmed not to act through generic changes in membrane permeability.
• Specificity testing: Validated against translation-associated antibiotics to distinguish true resistance mechanisms from non-specific effects.
• Ligand fishing workflow: His-tagged microprotein immobilized on an NTA sensor chip using Biacore surface plasmon resonance to capture interacting partners from yeast total protein extract.
• Partner identification: Bound proteins characterized by mass spectrometry, followed by functional bioassays to define interaction partners and mechanism of action.
• Translational goal: Extend the discovery pipeline to plant-derived microproteins involved in fungus-plant interactions for potential deployment in crop protection.

Technology readiness level

The technology is at an early discovery stage (TRL 2–3). A lead microprotein has been validated in yeast with demonstrated resistance to trichothecin, and specificity controls have been performed. The next phase involves Biacore-based ligand fishing, mass spectrometry identification of binding partners, and functional characterization of microprotein-protein interactions. Extension of the platform to identify plant microproteins with roles in fungal resistance represents the longer-term translational pathway toward agricultural applications.