Towards novel herbicide modes of action by inhibiting lysine biosynthesis in plants
journal contributionposted on 25.08.2021, 01:26 by Tatiana Soares-da-CostaTatiana Soares-da-Costa, Cody HallCody Hall, S Panjikar, Jessica WyllieJessica Wyllie, Rebecca ChristoffRebecca Christoff, S Bayat, Mark HulettMark Hulett, Belinda AbbottBelinda Abbott, Anthony GendallAnthony Gendall, Matthew PeruginiMatthew Perugini
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.