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

• Main Authors: 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
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-07-01
• Series: eLife
• Subjects: lysine; enzymes; herbicide
• Online Access: https://elifesciences.org/articles/69444

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.