ACCase inhibition

Whole plants were sprayed with a range of concentrations of the herbicides to determine the concentration needed to reduce growth by 50% (GR50) two weeks after application. As expected, soybean and red fescue plants were tolerant to both herbicides, wheat was resistant to tralkoxydim but not to haloxyfop, and the other species were susceptible (Table IV). The I50 data for ACCase inhibition reflected well the whole plant data. Soybean was most tolerant to the herbicides at both the whole plant and enzyme levels whereas maize was the most susceptible at both levels. The only notable exception was for wheat which, as expected, was tolerant to tralkoxydim but its ACCase was sensitive to inhibition. Thus, wheat tolerance is not due to insensitivity of its ACCase. 

Table IV. Effect of Haloxyfop and Tralkoxydim on Whole Plant Growth and ACCase Inhibition in Five Species...

I would like to thank Jake Secor for providing the ACCase inhibition data and Wendy Jacks for converting esters 2b-4b to the corresponding acids. 

DiODracarp Inhibition of lipid diesis - not ACCase inhibition TiocaibaniaiBS 30 3.4 150 470 1969... 

Fenoxaprop Aryloxypropionate Acetyl CoA carbox-ylase (ACCase) Inhibition of acetyl CoA carbox-ylase in fatty acid synthesis pathway 1984 Post- em gence Cereals Grasses, 200-500... 

D, whereas Nalewaja et a/. reported that exogenous applications of fatty acids and their esters enhanced rather than decreased the phytotoxicity of DM. Kocher et have also shown that the safener HOE 70542, which protects wheat from fenoxaprop-ethyl injury, did not influence the degree of ACCase inhibition by fenoxaprop-ethyl. 

A Inhibition of acetyl CoA carboxylase (ACCase) Aryloxyphenoxy- propionates Cyclohexanediones oximes 1... 

Fatty acid synthesis inhibitor, by inhibition of acetyl CoA Carboxylase (ACCase)... 

Aryloxyphenoxypropanoates and cyclohexanediones are two classes of herbicides that control many monocotyledoneous species. Although these herbicides are structurally very different (Fig. 1), there has been some conjecture that they have a similar mode of action because of their similarity in selectivity and symptomology. This paper describes the experiments that led to the discovery that aryloxyphenoxypropanoate and cyclohexanedione herbicides inhibit acetyl coenzyme A carboxylase (acetyl-coenzyme A bicarbonate ligase [ATP], EC 6.4.1.2) activity in susceptible species (1). In addition, evidence is presented indicating that the inhibition of acetyl coenzyme A carboxylase (ACCase) is well correlated to observed herbicidal activity. Similar, independent findings have recently been reported by two other research groups (2.3). 

The activity of ACCase extracted from maize was inhibited by both tralkoxydim and haloxyfop acid in a concentration dependant manner (Fig. 4). The concentration that inhibited activity by 50% (I50) was about 1 / M for both compounds. These values are similar to those recently reported by others (2.3). The methyl ester of haloxyfop was more than 100 fold less inhibitory than the free acid (Fig. 4), which is consistent with the methyl ester being deesterified in the plant. The data presented in Fig. 2 suggest that the deesterification occurs rapidly in leaf tissue. 

R(+) enantiomer is herbicidally active (23.24). Hoppe and Zacher (12) showed that the R(+) enantiomer of diclofop was more effective than the S(-) enantiomer in reducing acetate incorporation into free fatty acids in isolated maize chloroplasts. ACCase activity is inhibited by R(+) (98% enantiomeric excess) haloxyfop acid but not by the S(-) (94% enantiomeric excess) enantiomer (Fig. 5). The inhibition caused by the S(-) enantiomer could be accounted for by the 3% contamination in the S(-) preparation by the R(+) enantiomer. 

There are many other questions that need to be addressed. For example What are the kinetics of the inhibition Do the different inhibitors bind at the same site What are the molecular requirements for inhibition What are the differences between susceptible and tolerant ACCases and so on. ACCase purified 40 to 100 fold may not be sufficiently pure to answer many of these questions. For example, an extract purified on a Sephacryl S-300 column can have a specific activity up to 400 nmol/min/mg. We have observed that this preparation can catalyze the carboxylation of other short chained acyl CoA s in addition to acetyl CoA (Table VI). Both haloxyfop and tralkoxydim inhibit the carboxylation reaction regardless of whether n-propionyl CoA or acetyl CoA are substrates either individually or together (Table VII). At present, we are unsure whether n-propionyl CoA can be used as a substrate for ACCase or whether a n-propionyl CoA carboxylase is present in the preparation and the herbicides also inhibit that enzyme. 

One possible approach to developing new herbicides is to screen candidate molecules against both resistant and susceptible weeds, or the resistant and susceptible target enzymes from these weeds. This approach was used to identify novel ACCase inhibitors that inhibited the target enzyme from a collection of resistant and susceptible biotypes... 

ACCase prepared from the resistant L. multiflorum biotype, which had been selected by field use of didofop, was inhibited by the APPs diclofop, haloxyfop and quizalofop with IC50S (herbicide cone, needed for 50% enzyme inhibition) that were 28-, 9- and 10-times higher than for ACCase from a susceptible biotype. There was no cross-resistance to the CHD herbicides sethoxydim or dethodim [32]. ACCase resistance was subsequently also confirmed for L. multiflorum biotypes from other countries. In a resistant biotype selected by didofop in Normandy, the resistance factor (ratio of the IC50 for ACCase from the resistant to the IC50 for ACCase from the susceptible biotype) was 19 for diclofop and 5 for haloxyfop, but only 2 for the CHDs dethodim and sethoxydim [33]. Interestingly,... 

Recently PCR amplification and sequendng of plastidic ACCase domains involved in herbicide resistance has been employed to screen a spectrum of 29 grass spedes for target-site-based resistance to ACCase inhibitors by direct comparison of the sequences of plastidic ACCase around the critical codons [48]. The authors found that, in Poa annua and Festuca rubra, a leudne residue occurred at position 1781, while the wild types of all other grass spedes had an isoleucine in this position. Poa annua and F. rubra are already known from enzyme inhibition tests to possess a plastidic ACCase that is markedly less susceptible to ACCase inhibitors than the ACCase of other grass species. Thus, the leucine in position... 

Sethoxydim (e.g., Poast ) inhibits acetyl CoA carboxylase (ACCase) which is the first committed step in de novo fatty acid synthesis. SR corn was achieved by traditional breeding and selection for the herbicide insensitive ACCase allele and was introduced in 1996. SR corn accounted for less than 0.3% of corn acres in any one year and is no longer commercially available in field com (Fig. 6.1.4). 

In eukaryotes and prokaryotes, ACCase is a key enzyme in fatty acid biosynthesis [1]. The reaction product, malonyl-CoA, is both an intermediate in the de novo synthesis of primary fatty acids and also a substrate in the formation of long-chain fatty acids and flavonoids in plants [2, 3]. Aryloxyphenoxypropionates (APPs) and cyclohexandiones (CHDs) are two chemical classes of molecules that selectively inhibit homomeric, chloroplastic ACCase from grasses [4, 5], which makes them post emergent herbicides used worldwide to control grassy weeds. 

Since the multifunctional forms of plant ACCase function as dimers, we examined the binding to and subsequent inhibition of the enzyme by graminicides. Curve fits for the binding of quizalofop or fluazifop were generated for an equation of simple hyperbolic inhibition or the Hill equation. Maize ACCase 1 exhibited little cooperativity in binding graminicides but ACCase 2 (of reduced sensitivity) showed... 

A series of 2-(4-(1,X-naphthyridinyloxy)phenoxy)propan-oic acids were prepared for evaluation as potential grass herbicides and to assess their ability to inhibit maize acetyl-CoA carboxylase (ACCase). A new regiospecific pyridine annulation procedure was employed to prepare the key 2-chloro-l,6-, 1,7-, and 1,8-naphthyridine intermediates. Of the compounds prepared, only the 6-chloro-l,5-naphthyridinyloxyphen-oxy propanoic acid displayed substantial levels of herbicidal activity. The relative levels of herbicidal activity in this series of propanoic acids could be explained by the ability of these materials to inhibit ACCase. 

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