From bacteria to plants: a repurposing strategy in the pursuit for novel herbicides
Mackie, E.; Barrow, A.; Giel, M.-C.; Hulett, M. D.; Gendall, A.; Panjikar, S.; Soares da Costa, T.
Show abstract
Herbicide resistance represents one of the biggest threats to our natural environment and agricultural sector. Thus, new herbicides are urgently needed to tackle the rise in herbicideresistant weeds. Here, we employed a novel strategy to repurpose a failed antibiotic into a new and target-specific herbicidal compound. Specifically, we identified an inhibitor of bacterial dihydrodipicolinate reductase (DHDPR), an enzyme involved in lysine biosynthesis in plants and bacteria, that exhibited no antibacterial activity but severely attenuated germination of the plant Arabidopsis thaliana. We confirmed that the inhibitor targets plant DHDPR orthologues in vitro, and exhibits no toxic effects against human cell lines. A series of analogues were then synthesised with improved efficacy in germination assays and against soil-grown A. thaliana plants. We also showed that our lead compound is the first lysine biosynthesis inhibitor with herbicidal activity against a weed species, providing proof-of-concept that DHDPR inhibition may represent a much-needed new herbicide mode of action. Furthermore, this study exemplifies the untapped potential of repurposing failed antibiotic scaffolds to fast-track the development of herbicide candidates targeting the respective plant enzymes to combat the global rise in herbicide-resistant weeds.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Maramycin, a cytotoxic isoquinolinequinone terpenoid produced through heterologous expression of a bifunctional indole prenyltransferase /tryptophan indole-lyase in S. albidoflavus 96%
- Discovery of inhibitors for bacterial Arr enzymes ADP-ribosylating and inactivating rifamycin antibiotics 96%
- Repurposing of the RIPK1 selective benzooxazepin-4-one scaffold for the development of a type-III LIMK1/2 inhibitor 95%
Similar papers in this journal
- Structure and Mechanism of Avermitilol Synthase, a Sesquiterpene Cyclase that Generates a Highly Strained 6-6-3 Tricyclic Alcohol 95%
- Mechanism Underlying Anti-Markovnikov Addition in the Reaction of Pentalenene Synthase 94%
- Predicting antiviral resistance mutations in SARS-CoV-2 main protease with computational and experimental screening 94%
Similar papers in this journal
- Crystal structure of Fatty Acid Thioesterase A bound by 129 fragments provides diverse development opportunities 96%
- Can double PPO mutations exist in the same allele and are such mutants functional? 91%
- Characterisation of aphid antixenosis in aphid-resistant ancestor wheat, Triticum monococcum 91%
Similar papers in this journal
- Bacopa monnieri phytochemicals as promising BACE1 inhibitors for Alzheimers Disease Therapy 95%
- HTRF-based identification of small molecules targeting SARS-CoV-2 E protein interaction with ZO-1 PDZ2 95%
- Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.