Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants
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 cat...
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doaj-4a54238d54044027a2091d81d099209c2021-08-05T15:36:01ZengeLife Sciences Publications LtdeLife2050-084X2021-07-011010.7554/eLife.69444Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plantsTatiana P Soares da Costa0https://orcid.org/0000-0002-6275-7485Cody J Hall1Santosh Panjikar2https://orcid.org/0000-0001-7429-3879Jessica A Wyllie3Rebecca M Christoff4Saadi Bayat5Mark D Hulett6https://orcid.org/0000-0003-2072-5968Belinda M Abbott7Anthony R Gendall8https://orcid.org/0000-0002-2255-3939Matthew A Perugini9Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaAustralian Synchrotron, ANSTO, Clayton, Australia; Department of Molecular Biology and Biochemistry, Monash University, Melbourne, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaDepartment of Animal, Plant and Soil Sciences, AgriBio, La Trobe University, Bundoora, Australia; Australian Research Council Research Hub for Medicinal Agriculture, Bundoora, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, AustraliaWeeds 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 was 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.https://elifesciences.org/articles/69444lysineenzymesherbicide |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tatiana P Soares da Costa Cody J Hall Santosh Panjikar Jessica A Wyllie Rebecca M Christoff Saadi Bayat Mark D Hulett Belinda M Abbott Anthony R Gendall Matthew A Perugini |
spellingShingle |
Tatiana P Soares da Costa Cody J Hall Santosh Panjikar Jessica A Wyllie Rebecca M Christoff Saadi Bayat Mark D Hulett Belinda M Abbott Anthony R Gendall Matthew A Perugini Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants eLife lysine enzymes herbicide |
author_facet |
Tatiana P Soares da Costa Cody J Hall Santosh Panjikar Jessica A Wyllie Rebecca M Christoff Saadi Bayat Mark D Hulett Belinda M Abbott Anthony R Gendall Matthew A Perugini |
author_sort |
Tatiana P Soares da Costa |
title |
Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
title_short |
Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
title_full |
Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
title_fullStr |
Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
title_full_unstemmed |
Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
title_sort |
towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-07-01 |
description |
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 was 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. |
topic |
lysine enzymes herbicide |
url |
https://elifesciences.org/articles/69444 |
work_keys_str_mv |
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