ACETOLACTATE SYNTHASE, MECHANISM OF ACTION AND ITS HERBICIDE BINDING-SITE

Several new structurally diverse classes of herbicide, including the sulfonylurea herbicides, act by inhibiting acetolactate synthase, the first common enzyme of branched‐chain amino acid biosynthesis. The interaction of acetolactate synthase isozyme II (ALSII) from Salmonella typhimurium with sulfometuron methyl (SM), a sulfonylurea herbicide, has been used as a paradigm in elucidating the mode of action of these herbicides at the molecular level. A number of different studies have collectively suggested that SM binds to ALSII near thiamine pyrophosphate and flavin adenine dinucleotide (FAD), with its binding site overlapping the second pyruvate (or ketobutyrate) substrate site. Most of SM, however, must be accommodated on ALSII at a site that is not equivalent to substrate or co‐factor binding sites. The identity of this herbicide‐specific site has recently been suggested by the discovery that poxB, the gene for pyruvate oxidase, shares substantial sequence homology with ilvB, ilvG and ilvI, the genes for the large subunits of ALSI, ALSII, and ALSIII, respectively. Unlike ALSII, pyruvate oxidase uses its FAD for normal redox chemistry, and binds one additional co‐factor in vivo, ubiquinone‐40. The latter co‐factor binds to pyruvate oxidase in a spatially and kinetically equivalent way to SM with ALSII, suggesting that the herbicide binding site of ALSII has a common evolutionary heritage with the ubiquinone site of pyruvate oxidase. Copyright © 1990 John Wiley & Sons, Ltd