ABSTRACT
The discovery of acetolactate synthase (ALS; also known as acetohydroxy acid synthase; AHAS) as the site of action of the sulfonylurea and imidazolinone herbicides (LaRossa and Schloss 1984; Ray 1984; Shaner et al. 1984) prompted the search for new herbicides that targeted ALS as well as other enzymes in branched-chain amino acid biosynthesis (see Chap. 7 for details on the pathway). These studies have produced several new classes of inhibitors for ALS (Saari et aI. 1994; Singh and Shaner 1995b) as well as inhibitors for almost every step in the pathway. Biochemical and physiological studies conducted in the search for new herbicides have provided a wealth of information on the chemical mechanism of these enzymes and the effects of their inhibition in vivo. In addition, studies with the herbicidal inhibitors of ALS have provided information on the mechanisms for crop selectivity and the basis for the appearance of weed resistance. Although inhibitors of ALS remain the only commercial herbicides that target branchedchain amino acid biosynthesis, there is good evidence that most of the inhibitors of the other steps cause physiological responses in plants by inhibiting their respective target enzymes in vivo. However, in the latter, the amount of compound required to control weeds is significantly higher than that of the ALS inhibitors. thereby decreasing their usefulness as commercial herbicides. Several investigations offer explanations for these differences in potency. Together, these studies have helped formulate the characteristics of an ideal enzyme target for herbicides and other pesticides (Abell 1996). They have also made it very clear that the chemical inhibition of an enzyme (in the range of 60-90% inhibition) in a critical pathway is not necessarily lethal. The extent of inhibition, the mechanism of inhibition, and the amount of excess enzyme capacity, all are factors that determine whether inhibition of a target will lead to herbicidal activity. The purpose of this chapter is to summarize the inhibitor studies on the enzymes of this pathway that have helped shape our understanding of these sites as targets for the design of new herbicides.
