Aryloxyphenoxypropionates and Cyclohexanediones

The aryloxyphenoxypropionates and cylcohexanediones are two important classes of grass-selective herbicides which have been developed 

Early work on aryloxyphenoxypropionates failed to show any metabolic effects except those on acyl lipid synthesis. The general inhibition of labeling of all acyl lipid classes but not that of sterols or terpenoids led to the idea that de novo fatty acid synthesis was being reduced. In fact, there is little effect on fatty acid elongation (e.g.. Table 3.13). Of the two enzyme systems involved in de novo synthesis, it has now been established that the aryloxyphenoxypropionates and cyclohexanediones only affect acetyl-CoA carboxylase. Moreover, this carboxylase from dicotyledons (resistant) appears to be different from that in monocotyledons (sensitive) because the selectivity of herbicides (including stereospecificity) is retained during in vitro measurements (Table 3.14). 

Comparisons of relative activities of aryloxyphenoxypropionates on acetyl-CoA carboxylase measured in vitro with results from whole-plant 

Just as wheat appeared to be tolerant toward diclofop at the whole-plant but not the enzyme level, because of selective inactivation, so various fescue grasses have been shown to be tolerant. At the chloroplast level, the sensitivity of Festuca ovina and F. rubra toward diclofop was comparable to that of the sensitive P. arundinacea The resistance to diclofop in vivo appears to be due to metabolism of the herbicide to less active compounds, as in wheat. By contrast, F. ovina and F. rubra are also resistant to cycloxydim, but, in that case, fatty acid synthesis by isolated chloroplasts is also relatively unaffected (I50 about 100 pM). There may be some differences in the acetyl-CoA carboxylase protein structure in these species that renders cycloxydim binding less effective than usual. 

In view of the large difference in structure between cyclohexanediones and aryloxyphenoxypropionates, it would be rather surprising if all acetyl-CoA carboxylases showed equal sensitivity or resistance against these herbicide classes. It has also been found that Lolium multiflorum L. is resistant toward diclofop but sensitive toward sethoxydim and that this difference 

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Figure 3.8. Structures of some aryloxyphenoxypropionates and cyclohexanediones that have been shown to inhibit acetyl-CoA carboxylase in sensitive species.

A third class of chemical has recently been shown to produce similar effects to those of the aryloxyphenoxypropionates and cyclohexanediones. This herbicide, PP600 3-isopropyl-6-[AT-(2,2-dimethylpropyl)acetamido]-l,3,5-triazine-2,4(lf/,3//)-dione, was shown to inhibit fatty acid synthesis in monocotyledons, but not dicotyledons, having an I50 value of about 1 fxM for barley. Although acetyl-CoA carboxylase was inhibited by PP600, the enzyme was much less sensitive than whole-tissue preparations, raising the possibility that PP600 is metabolized to a more active metabolite in vivo. ... 

There are a number of factors which can contribute to herbicide selectivity, including soil placement, rates of absorption and subsequent translocation, localization (both within the plant and at the subcellular level), and transformation to products of modified phytotoxicity. In addition, the recent work on the elucidation of the modes of action of the aryloxyphenoxypropionate and cyclohexanedione groups of herbicides has highlighted the importance of species differences in sensitivity of the target site, in this case the enzyme acetyl-CoA carboxylase. The monocot and dicot enzymes studied to date show a remarkable difference in sensitivity to these herbicides which correlates very well with the high level of resistance among dicots. Biotypes of Chenopodium album and Amaranthus hybridus L. resistant to atrazine as a result of a mutation in the 32-kDa protein component of photosystem II would constitute a further example. 

It appears that resistance to the aryloxyphenoxypropionate herbicides, the cyclohexanedione herbicides and to the sulfonylurea herbicides is unlikely to be due to reductions in the sensitivity or increases in the amounts of their respective target enzymes (Figures 2 3). Studies have not yet been performed to examine if die resistance to the dinitroaniline herbicide trifluralin is associated with any change at the tubulin polymerization site. 

The best characterized extraneous site ir bitors are the many chemical classes of herbicidal inhibitors of acetolactate synthase. These have been extensively reviewed elsewhere (i, 8,9,52,56,81,92). Extraneous site inhibitors are also exemplified by four classes of grass selective herbicides the aryloxyphenoxypropionic acids represented by diclofop, the cyclohexanediones typified by clethc m (for a recent review see (57)), the triazinediones (82) and the perhydroindolizinediones (83) (Figure 7). The following discussion is limited to the first two classes. Both classes of herbicides are potent, reversible inhibitors of acetyl-CoA carboxylase (ACC) from susceptible plants, the putative rate limiting enzyme in lipid biosynthesis. With wheat... 

FIuazifop (2-[4-(5-trifluoromethyl-2-pyr1dyloxy)phenoxy]propionate) is a grass-specific herbicide. It is an aryloxyphenoxypropionate compound and these herbicides have been shown to kill sensitive species by causing necrosis of meristematic tissues. A number of studies on the mode of action of the aryloxyphenoxypropionates have only been able to demonstrate an inhibition of lipid metabolism. No detectable effects on CO2 fixation or carbohydrate, amino acid or nucleic acid metabolism have been shown ( Walker 1988a,). Cyclohexanedione herbicides, such as sethoxydim,... 

Burton JD, Gronwald JW, Somers DA, Connelly JA, Gengenbach BG, Wyse DL. Inhibition of plant acetyl-coenzyme A carboxylase by the herbicides Sethoxydim and Haloxyfop. Biochem Biophys Res Comm 1987 148 1039-1044. Parker WB, Marshall LC, Burton JD et al. Dominant mutations causing alterations in acetyl-coenzyme A carboxylase confer tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides in maize. Proc Natl Acad Sci USA 1990 87 7175-7179. 

A number of biotin-containing enzymes have now been demonstrated in plants. If cyclohexanediones and aryloxyphenoxypropionates interfere with the carboxyltransferase reaction of acetyl-CoA carboxylase, one would... 

In summary, the cyclohexanediones and aryloxyphenoxypropionates are herbicidal because they inhibit the carboxyltransferase partial reaction of acetyl-CoA carboxylase in sensitive plants. Their selectivity appears to be based on structural differences in the target enzyme, and this raises fundamental questions about protein sequence and conformation as well as offering some attractive possibilities for gene manipulation. ... 

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