Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants
- La Trobe University, Australia
- Australian Synchrotron, Monash University, Australia
Abstract
Weeds are becoming increasingly resistant to our current herbicides, posing a significant threat to agricultural production. Therefore, new herbicides with novel modes of action are urgently needed. In this study, we exploited a novel herbicide target, dihydrodipicolinate synthase (DHDPS), which catalyses the first and rate-limiting step in lysine biosynthesis. The first class of plant DHDPS inhibitors with micromolar potency against Arabidopsis thaliana DHDPS were identified using a high throughput chemical screen. We determined that this class of inhibitors binds to a novel and unexplored pocket within DHDPS, which is highly conserved across plant species. The inhibitors also attenuated the germination and growth of A. thaliana seedlings and confirmed their pre-emergence herbicidal activity in soil-grown plants. These results provide proof-of-concept that lysine biosynthesis represents a promising target for the development of herbicides with a novel mode of action to tackle the global rise of herbicide resistant weeds.
Data availability
Diffraction data have been deposited in PDB under the accession code 7MDS. The validation report has been uploaded as a 'Related Manuscript File'.Other data sets have been uploaded as 'Source Data' files.
Article and author information
Author details
Tatiana P Soares da Costa
Funding
National Health and Medical Research Council (APP1091976)
- Tatiana P Soares da Costa
Australian Research Council (DE190100806)
- Tatiana P Soares da Costa
Australian Research Council (DP150103313)
- Santosh Panjikar
- Matthew A Perugini
Australian Research Council Research Hub for Medicinal Agriculture (IH180100006)
- Anthony R Gendall
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Todd Gaines, Colorado State University, United States
Version history
- Received: April 15, 2021
- Preprint posted: May 6, 2021 (view preprint)
- Accepted: July 27, 2021
- Accepted Manuscript published: July 27, 2021 (version 1)
- Version of Record published: August 5, 2021 (version 2)
Copyright
© 2021, Soares da Costa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants
eLife 10:e69444.
https://doi.org/10.7554/eLife.69444
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