The discovery of a novel site of action for herbicidal bisphosphonates

Following renewed interest in a class of herbicides containing a 1,1-bispho sphonate moiety, studies to identify the molecular target for these compoun ds were initiated. N-(2-(3-methylpyridyl)) aminomethylene diphosphonic acid (compound I), a representative example of this group, was found not to inh ibit soluble plant pyrophosphatases or H+-translocating pyrophosphatases in the vacuolar membrane. Fatty acid biosynthesis from acetate or from pyruva te was also not suppressed by this herbicide. Germination of plant seeds wa s not inhibited by the bisphosphonate, but root growth in the dark was stro ngly inhibited without a significant effect on respiration. The bisphosphon ate had little effect on nucleic acid biosynthesis. However, the biosynthes is of carotenoids from isopentenyl pyrophosphate in daffodil (Narcissus sp. ) chromoplasts was found to be strongly inhibited by compound I at 2.5 mu M . Further study showed that isopentenyl pyrophosphate:dimethylallylpyrophos phate isomerase was not blocked by the compound but that farnesyl pyrophosp hate synthase was very strongly inhibited by compound I with an IC50 of 23 nM. It is proposed that bisphosphonates such as compound I are herbicidal a s a result of the inhibition of farnesyl pyrophosphate synthase in the pren yl biosynthetic pathway and that this enzyme represents a new target site f or the development of herbicides. (C) 1999 Academic Press.