Protoporphyrinogen Oxidase as the Optimal Herbicide Site in the Porphyrin Pathway

Abstract

Herbicide discovery efforts have yielded a large number of excellent herbicides that target the porphyrin pathway. Protoporphyrinogen oxidase (Protox) is the only molecular site inhibited by the commercially available members of this herbicide class. We hypothesize that this site of action is much better for herbicidal activity than other sites of the porphyrin pathway because of the location of herbicide-susceptible Protox within the cell (the plastid envelope and the mitochondrion), the existence of a herbicide-resistant form of the enzyme in the plasma membrane (which rapidly causes accumulation of protoporphyrin IX when plastid Protox is inhibited), and two chemical features of the substrate (its relatively low lipophilicity and its non-planar macrocycle). Although enzymes of the porphyrin pathway beyond Protox can be inhibited to cause the accumulation of phytotoxic levels of porphyrins, these sites do not share the unique properties of Protox. As a result, the number of active analogues that effectively inhibit these enzymes in vivo is much smaller than for Protox, and the amount of herbicide needed for effective herbicidal action is relatively higher.Thousands of herbicides have been patented that apparently exert their phytotoxicity through induced accumulation of phototoxic porphyrins (I, 2). All of those for which the molecular site of action is known are inhibitors of protoporphyrinogen oxidase (Protox), the last enzyme common to the synthesis of both chlorophyll and heme in green plants (J, 3-8). Theoretically, inhibition of any enzyme of the porphyrin pathway ( Figure 1; see Figure 1 of Chapter 1 for structures of intermediates) past porphobilinogen deaminase (uroporphyrinogen III cosynthase) would result in the accumulation of a photodynamic porphyrin. Sites in the 0097-6156/94/0559-0191$08.00/0

Design, synthesis and herbicidal activity of novel sulfonylureas containing tetrahydrophthalimide substructure

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Synthesis and herbicidal activity of 1,3-substituted quinazolinedione derivatives

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