ACCase

Acetyl-CoA carboxylase (ACCase) carboxylates acetyl-CoA into malo-nyl-CoA and therefore represents the first committed step in fatty acid biosynthesis. ACCase is a multimer essential for cell growth whose components are highly conserved among bacteria, making it a promising broad-spectrum target [8]. 

Rice appears to be tolerant to quinclorac by having an ACCase that is not as affected by the herbicide as well as having a high b-cyano-alanine synthase activity. ... 

Copper-dependent enzymes, ASCORBATE OXIDASE CATECHOL OXIDASE FERROXIDASE GAACTOSE OXIDASE ACCASE... 

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

Heap (1999) accurately predicted that due to the economic importance of ALS and ACCase inhibitor herbicides worldwide and the ease with which weeds become resistant to them, it is likely that the weeds resistant to these herbicides will present farmers with greater problems in the next 5 years than triazine-resistant weeds have in the past 25 years. 

Most of the ALS and ACCase herbicides have been introduced and used commercially only within the past 10-15 years and are often used repeatedly on the same land area. For example, several ALS inhibitors are used on com, while others in this class are used on soybean. Even though the crops are rotated and different herbicides are used, the different herbicides have the same mode or site of action, which increases the selection pressure for resistant weed populations. Various ALS inhibitors are now being used in many crops, including com, sorghum, soybean, and cereal grain. 

Hall et al. (1998) reported that an ALS-resistant biotype of false cleavers was cross-resistant to a broad range of ALS inhibitors, as well as to an auxin-type herbicide, quinclorac, which had never before been applied to these fields. A similar case of quinclorac multiple resistance in smooth crabgrass has been reported in California when plants were previously treated with ACCase herbicides. Data suggest a target site-based mechanism of resistance involving the accumulation of cyanide derived from stimulated ACC synthesis, which is a precursor of ethylene (Abdallah et al., 2004). 

Yu, Q., A. Caims, and S.B. Powles (2007). Glyphosate, paraquat, and ACCase multiple resistance in a Lolium rigidum biotype. Plants, 225 499-513. 

Average effect of emodin analogue (series 1) on (0.03 - 1000 pM) on chlorophyll concentration in ACCase resistant Avena sp. (- -) and Agrostis sp. (-o-) after 7 days of growth. 

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 pathway from acetate to palmitic acid (actually a palmitic acid-acyl carrier protein complex) involves at least nine enzymes acetyl CoA synthetase, acetyl CoA carboxylase, and the seven enzyme fatty acid synthetase complex. We chose first to test the effect of these compounds on acetyl CoA carboxylase (ACCase) activity. There were several reasons to select ACCase as the... 

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. 

A comparision of five aryloxyphenoxypropanoate herbicides shows that they are very active inhibitors of maize ACCase (Table III). The I50 values range from less than 25 nM for quizalofop to about 3 /zM for fluazifop. The I50 values are not necessarily well correlated with whole plant activity. For example, diclofop has a higher recommended use rate than does haloxyfop, yet diclofop is about three times more active at the enzyme level. A reason for this discrepancy is that the outer benzene ring of diclofop can be readily hydroxylated in plant tissue to form a herbicidally less active molecule (25). 

Table III. Effect of Five Aryloxyphenoxypropanoate Herbicides on Maize ACCase Activity...

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...

Once that it was established that ACCase was a target site of the aryloxyphenoxypropanoates and cyclohexanediones, we began to investigate the relationship between the herbicides and the enzyme. Using a protein extract prepared as previously described (1) and further purified through a Sephacryl S-300 gel filtration column, we determined whether the inhibitors were covalently bound... 

Table V. Effect of Desalting an ACCase-Herbicide Mixture on Enzyme Activity...

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. 

Figure 6. Results of SDS polyacrylamide gel electrophoresis on the supernatant of a crude maize extract (A), a 6 to 14 % polyethylene glycol precipitate (B), and pooled fractions having ACCase activity from a Sephacryl S-300 column (C).

To examine the purity of the protein that was eluted from a Sephacryl S-300 column, we subjected the protein to SDS polyacrylamide gel electrophoresis (SDS-PAGE) and then performed a Western blot (26) using avidin linked to phosphatase as a probe. The SDS-PAGE indicated that there were many polypeptides in this partly purified preparation (Fig. 6). Among these were two major and several minor biotin-containing bands (Fig. 7). This preparation may contain propionyl CoA carboxylase or a partly degraded form of ACCase that can use propionyl CoA as well as acetyl CoA as a substrate. Therefore, the enzyme data presented here are quali-... 

Surprises or unpredicted events can happen. The early dogma, also based largely on our experience of triazine resistance, suggested that soil residual activity of herbicides was an important, if not essential, contributor to the selection of resistant biotypes. The subsequent development of multiple instances of paraquat resistance, followed by resistance to acetyl CoA carboxylase (ACCase) inhibitors, demonstrated that soil activity was not necessary for resistance to evolve. 

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