With rapid progress being made in deciphering plant genomic sequences, determining the function of these genes is one of the main challenges that plant molecular biologists face today. Herbicidal inhibitors have been very useful for understanding gene function in at least two examples, represented by herbicidal inhibitors of hydroxyphenylpyruvate dioxygenase (HPPD) and deoxyxylulosephosphate reductoisomerase (DXR). In the first, an albino mutant of Arabidopsis isolated during the study of carotenoid biosynthesis was found to have an intact carotenoid biosynthetic pathway. A number of “bleaching herbicides” in development at about the same time (e.g., sulcotrione) produced similar symptoms by strongly inhibiting HPPD, a key enzyme in plastoquinone biosynthesis. Examination of the Arabidopsis mutant revealed that the HPPD gene had been inactivated in the albino plants. Inhibition of the HPPD pathway also led to reduced levels of tocopherol (vitamin E), an end product of the pathway. Further studies and manipulation of the pathway produced plants with significantly higher levels of vitamin E. This result is a clear demonstration of how an herbicidal inhibitor was able to lead to the identification of a gene that was responsible for a particular phenotype. As a second example, identification of fosmidomycin as a specific inhibitor of DXR in the recently elucidated nonmevalonate pathway of isopentenyl pyrophosphate (IPP) biosynthesis was instrumental in furthering the understanding of an important route to synthesis of many important terpenoid products.
Nomenclature: Fosmidomycin, 3-(N-formyl-N-hydroxyamino)propylphosphonic acid; sulcotrione; Arabidopsis mutant.