Validation of the HRAC classification of inhibitors of the synthesis of very long-chain fatty acids
Herbicides are essential tools in modern agriculture for controlling weeds and safeguarding crop productivity. To aid resistance management, the Herbicide Resistance Action Committee (HRAC) classifies herbicides based on their mode of action (MoA). In 2020, herbicides previously grouped as classes N and K3 were reclassified into HRAC Group 15, which targets very-long-chain fatty acid (VLCFA) biosynthesis. While the molecular targets of former class K3 herbicides are well-characterized, the MoA of class N herbicides—particularly thiocarbamates—remains unconfirmed. In this study, we hypothesize that sulfoxidated thiocarbamates inhibit 3-oxoacyl-CoA synthases (keto-acyl-CoA synthases, KCSs), the condensing enzymes of the VLCFA elongation complex. To test this, we analyze RNA-Seq data from seedlings of various weed species to identify and select KCS isoforms highly expressed in seedlings. These candidates are heterologously expressed in Saccharomyces cerevisiae, and the engineered yeast strains are treated with sulfoxidated thiocarbamates. VLCFA profiles are subsequently examined using gas chromatography-mass spectrometry (GC-MS). The elucidation of the mechanism of action of thiocarbamates improves the classification of herbicides and enables more effective resistance management in agricultural practice.
Project team:
- Rebecka Dücker (Principal Investigator, Georg-August Universität Göttingen)
- Mohit Mahey (visiting scholar from Michigan State University)