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1177133_SoaresdaCosta,T_2021.pdf (2.91 MB)

Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants

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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.

Funding

National Health and Medical Research Council of Australia 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 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.

History

Publication Date

01/07/2021

Journal

eLife

Volume

10

Article Number

ARTN e69444

Pagination

17p.

Publisher

ELIFE SCIENCES PUBLICATIONS LTD

ISSN

2050-084X

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