Although several commercial herbicides inhibit amino acid production in plants, lysine biosynthesis is yet to be exploited as a herbicide mode of action. We have developed the first herbicidal inhibitors of lysine biosynthesis, which target the first enzyme in the pathway, DHDPS. We have shown that these compounds exhibit potent in vitro and in planta activity using enzyme kinetic and herbicidal activity assays, whilst lacking off-target effects as demonstrated by cytotoxicity and antibacterial assays. Using X-ray crystallography, we have revealed that these inhibitors bind in a novel allosteric site in DHDPS, which is highly conserved across plant species. Interestingly, we noted that this class of inhibitors has an additional mode of action through inhibition of the second enzyme in the lysine biosynthesis pathway, DHDPR, using enzyme kinetic assays and in silico docking. This inhibitor class represents the first example of dual-target herbicidal compounds, which may have a reduced susceptibility to the generation of resistance. Additionally, this is the first time that an inhibitor with allosteric and orthosteric activity at two different enzymes has been reported. This work has the potential to contribute novel herbicide modes of action and strategies to mitigate resistance to help combat the rise in herbicide resistant weeds globally.

Towards herbicides with new modes of action by targeting lysine biosynthesis

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.