Inhibition of saturated very-long-chain fatty acid biosynthesis by mefluidide and perfluidone, selective inhibitors of 3-ketoacyl-CoA synthases

► The mode of action of mefluidide and perfluidone was studied. ► Physiological and metabolic profiling indicate a primary MoA in VLCFA biosynthesis. ► We have expressed seven active 3-ketoacyl-CoA synthases in an in vivo yeast system. ► Mefluidide and perfluidone inhibit KCS activity in the micro molar range. ► The AtCER6 protein is highly sensitive to compound inhibition.