NEW TARGET ENZYME(S) FOR BISPHOSPHONATES - INHIBITION OF GERANYLGERANYL DIPHOSPHATE SYNTHASE

Bisphosphonates, exemplified by CGA 103586 (Patent of Nissan; U.S., 4, 447,256; Germany, 28 31 578), are a class of herbicides with excellent activity after stem injection. Their in vivo activity is weak due to uptake problems of compounds containing to highly polar phosphonate mo ieties. The mode of action of bisphosphonates was until now controvers ial. Our results clearly show that a group of bisphosphonates inhibit the chlorophyll- and carotenoid-biosynthesis pathways by blocking gera nylgeranyl diphosphate synthase without interfering with the shikimate pathway as previously published. Besides this main effect the bisphos phonates examined in this study inhibit to a lesser extent squalene sy nthase and phyloene synthase which is not critical for herbicidal acti vity. The unique enzyme inhibition pattern reported here constitutes, to our knowledge, a new mode of action. (C)1998 Academic Press.