Direct and selective small‐molecule inhibition of photosynthetic PEP carboxylase: New approach to combat C 4 weeds in arable crops

Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme of C 4 photosynthesis. Besides, non‐photosynthetic isoforms of PEPC are found in bacteria and all types of plants, although not in animals or fungi. A single residue in the allosteric feedback inhibitor site of PEPC was shown to adjust the affinity of the photosynthetic and non‐photosynthetic isoforms for feedback inhibition by metabolites of the C 4 pathway. Here, we applied computational screening and biochemical analyses to identify molecules that selectively inhibit C 4 PEPC, but have no effect on the activity of non‐photosynthetic PEPCs. We found two types of selective inhibitors, catechins and quinoxalines. Binding constants in the lower μM range and a strong preference for C 4 PEPC qualify the quinoxaline compounds as potential selective herbicides to combat C 4 weeds.