Inhibition profile of trifludimoxazin towards PPO2 target site mutations

Abstract

BACKGROUND Target site resistance to herbicides that inhibit protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) has been described mainly in broadleaf weeds based on mutations in the gene designated protoporphyrinogen oxidase 2 (PPO2) and in one monocot weed species in protoporphyrinogen oxidase 1 (PPO1). To control PPO target site resistant weeds in future it is important to design new PPO‐inhibiting herbicides that can control problematic weeds expressing mutant PPO enzymes. In this study, we assessed the efficacy of a new triazinone‐type inhibitor, trifludimoxazin, to inhibit PPO2 enzymes carrying target site mutations in comparison with three widely used PPO‐inhibiting herbicides. RESULTS Mutated Amaranthus spp. PPO2 enzymes were expressed in Escherichia coli, purified and measured biochemically for activity and inhibition kinetics, and used for complementation experiments in an E. coli hemG mutant that lacks the corresponding microbial PPO gene function. In addition, we used ectopic expression in Arabidopsis and structural PPO protein modeling to support the enzyme inhibition study. The generated data strongly suggest that trifludimoxazin is a strong inhibitor both at the enzyme level and in transgenics Arabidopsis ectopically expressing PPO2 target site mutations. CONCLUSION Trifludimoxazin is a potent PPO‐inhibiting herbicide that inhibits various PPO2 enzymes carrying target site mutations and could be used as a chemical‐based control strategy to mitigate the widespread occurrence of PPO target site resistance as well as weeds that have evolved resistance to other herbicide mode of actions. © 2022 BASF SE and The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Discovery, mode of action, resistance mechanisms, and plan of action for sustainable use of Group 14 herbicides

“…Trifludimoxazin had very good efficacy against PPO-resistant Amaranthus biotypes possessing the G210 deletion (Figure 11); 12 g ha −1 and 18 g ha −1 of trifludimoxazin resulted in 88% and 96% control of an Amaranthus ΔG210 biotype, respectively, while saflufenacil and lactofen at 50 g ha −1 and 420 g ha −1 , respectively, provided less than 50% control. These results suggest that trifludimoxazin can be used to control PPO-resistant biotypes with currently known target-site mutations (Porri et al 2023).…”

“…Trifludimoxazin has novel properties that contribute to a more stable binding compared with other PPO-inhibiting herbicides. One feature is complementary shape between ligand and protein, leading to many favorable van der Waals interactions (Porri et al 2023). In addition, the molecule is stabilized by pi-stacking effects of the ring systems.…”

Novel Artificial Intelligence platform leads to the discovery of new protoporphyrinogen oxidase inhibitors

“…While some weeds have evolved resistance to certain PPO-inhibiting chemistry, group 14 herbicides remain an important group of chemicals to manage weeds, 26-28 and many major agrochemical companies are developing new molecules with this mode of action. 29,30 The Agresense algorithm continues to identify novel chemical spaces with potentially new MoAs.…”

Design, Synthesis, and Metabolism Studies of N-1,4-Diketophenyltriazinones as Protoporphyrinogen IX Oxidase Inhibitors

“…Trifludimoxazin and epyrifenacil are all nonselective herbicides developed by BASF and Sumitomo Chemical Co., Ltd., respectively . What’s unique to other PPO inhibitory herbicides is that trifludimoxazin can control some PPO herbicide-resistant weeds, such as Amaranthus species. − Studies have shown that PPO inhibitory herbicides have larger interaction volumes with PPO that similar to the substrate protoporphyrinogen IX would exhibit higher resistance levels than compounds with smaller interaction volumes . Trifludimoxazin has a novel warhead (6-thioxo-1,3,5-triazinane-2,4-dione), which is different from the other PPO inhibitors. ,− This unique structure may also contribute to its excellent herbicidal performance …”