Screening marine fungi for inhibitors of the C4 plant enzyme pyruvate phosphate dikinase:: Unguinol as a potential novel herbicide candidate

A total of 2,245 extracts, derived from 449 marine fungi cultivated in five types of media, were screened against the C-4 plant enzyme pyruvate phosphate dikinase (PPDK), a potential herbicide target. Extracts from several fungal isolates selectively inhibited PPDK. Bioassay-guided fractionation of one isolate led to the isolation of the known compound unguinol, which inhibited PPDK with a 50% inhibitory concentration of 42.3 +/- 0.8 mu M. Further kinetic analysis revealed that unguinoll was a mixed noncompetitive inhibitor of PPDK with respect to the substrates pyruvate and ATP and an uncompetitive inhibitor of PPDK with respect to phosphate. Unguinoll had deleterious effects on a model C-4 Plant but no effect on a model C-3 plant. These results indicate that unguinol inhibits PPDK via a novel mechanism of action which also translates to an herbicidal effect on whole plants.