Scientists are turning to innovative strategies in the face of mounting herbicide resistance threatening agriculture and the natural environment. For example, a study published in 2023 by Emily et al. introduced a unique method of repurposing an unsuccessful antibiotic into a novel, target-specific herbicidal compound.
The research team identified an inhibitor of the bacterial enzyme dihydrodipicolinate reductase (DHDPR), a crucial participant in lysine biosynthesis in both plants and bacteria. Interestingly, while the inhibitor displayed no antibacterial activity, it significantly hampered the germination of Arabidopsis thaliana.
The inhibitor’s safety profile was further established through tests on human cell lines, which showed no toxic effects. Finally, in vitro experiments confirmed that the inhibitor targets DHDPR orthologues in plants, demonstrating its specific activity.
The researchers created a series of analogs of the inhibitor, which showed enhanced effectiveness in germination assays and against soil-grown A. thaliana. Most notably, the lead compound from this series emerged as the first lysine biosynthesis inhibitor with activity against both monocotyledonous and dicotyledonous weed species.
Tests of this lead compound proved its efficacy in reducing the germination and growth of Lolium rigidum (rigid ryegrass) and Raphanus raphanistrum (wild radish), two problematic weed species. These results present a convincing case that DHDPR inhibition could serve as a new herbicide mode of action, providing a much-needed weapon in the fight against herbicide resistance.
The findings also underscore the potential of repurposing ‘failed’ antibiotic structures to expedite the development of herbicide candidates targeting specific plant enzymes. While promising, the research team noted the need to further explore this innovative approach in a broader range of plant species and environmental conditions.
Photo by James Baltz on Unsplash
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