Seaweed-based PPO inhibitors as a new frontier in biological weed control for sorghum cultivation: from ocean to field.

Weed management, particularly of broad-leaf species, poses a significant challenge in sorghum production, potentially causing up to 70.9% yield loss. Conventionally, herbicides are the site-specific weed inhibitors often used to suppress the growth of these weeds. Protoporphyrinogen oxidase (PPO) is an important target for developing novel herbicides with remarkable selectivity against these broad-leaved weeds. In particular, saflufenacil is a selective PPO herbicide that can provide temporary relief. However, their prolonged use could lead to various environmental constraints and the evolution of resistant weeds. Recently, bioherbicides are emerging as an alternative to commercial herbicides with safer environmental profiles and combat resistance. On that note, this study aimed to identify novel and safer bioherbicides derived from seaweeds to outright bans on the use of most synthetic herbicides and address herbicide resistance. High-end computational screening strategies including molecular docking, binding free energy, in-house developed ML-based VS, and herbicide-likeness were used to pinpoint the lead molecule against the wild and mutant (∆G210) type AtPPO. Finally, molecular dynamics simulations were employed to validate the binding kinetics of the hit compound. Indeed, the bromophenol derivative BL003, isolated from brown algae, emerged as the hit compound from our analysis. Remarkably, BL003 demonstrated superior binding affinity and stability compared to saflufenacil against both wild-type AtPPO and the mutant AtPPO. Thus, our findings could open new avenues for developing sustainable, seaweed-derived herbicides for sorghum cultivation. This research could contribute to the ongoing efforts to create environmentally friendly weed management solutions in agriculture.