ACCase Inhibitors

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]. 

---

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. 

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. 

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 Inhibitors - ALS Inhibitors <-Dinitroanilines i Triazines - -Ureas, Amides — Bipyridyliums - -Synthetic Auxins — Glycines... 

Target-site resistance of biotypes to ACCase inhibitors has up to now been confirmed for quite a few grass weed species of economic importance. The earliest cases of target-site based resistance were reported for biotypes of LoUum multi-Jlorum from Oregon, USA [30] and of LoUum rigidum from Australia [31]. 

First biotypes of LoUum ri um with target-site resistance to ACCase inhibitors were identified in the early 1990s in Australia. Sdection either with an APP or a CHD herbicide resulted in target-site cross-resistance to both herbicide groups. But, regardless of whether selection was by an APP or a CHD compound, the level of resistance in these biotypes was higher to APP than to CHD herbicides. ACCase resistance factors were 30-85 for diclofop, >10-216 for haloxyfop and 1-8 for sethoxydim [31, 35, 36]. 

Biotypes with target-site-based resistance to ACCase inhibitors were also selected in wild oat species [Avena fatua, A. sterilis). The resistance patterns were found to be variable. For example, the resistance factors for ACCase from the Canadian A. fatua biotype UMl were 105 for sethoxydim, 10 for tralkoxydim, and 10 for didofop and fenoxaprop, whereas for the Aoena fatua biotype UM33 from Canada the ratios were 10.5 for fenoxaprop, 1.2 for diclofop, 5 for sethoxydim and 1.7 for tralkoxydim. It was proposed that this was due to different point mutations, each being assodated with a characteristic resistance pattern [37]. Another reason could be the frequency of homozygote and heterozygote resistant and susceptible plants within a tested population. 

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... 

Cloquintocet-mexyl was developed under the code CGA 185072 by Ciba-Geigy (now Syngenta) and is used post-emergence in cereals. The basic patent (EP 94349) has a priority date of 7 May 1982. Various other country patents followed (e.g., US4902340 and US 5102445). It was first reported in 1989 [13] alongside the ACCase inhibitor clodinafop-propargyl, and till now the main use of... 

Expression of an herbicide insensitive target has also been reported to provide resistance to diclofop and sethoxydim (ACCase inhibitors), various dinitroani-lines, and inhibitors of phytoene desaturase, lycopene cyclase and hydroxyphenyl-pyruvate dioxygenase. None of these traits are currently incorporated into commercial products. 

Discovery of the Cyclic Ketoenois, Spirodiclofen and Spiromesifen as a New Generation of ACCase Inhibitors... 

The physical properties of pyridine-containing acids make them particularly attractive starting points for combinatorial libraries for herbicide screens. Pyridines are relatively polar (log P = 0.60 for pyridine vs. 2.13 for benzene) (4) and the sinq>le unsubstituted acids are weakly acidic (nicotinic acid pKa 4.8). (5) Perhaps for these reasons, pyridine-containing acids have found considerable utility as herbicides. Representative examples of commercially successful, phloem mobile, pyridine acids (or dieir derivatives) include picloram, clopyralid, and triclopyr (synthetic auxins) imazethapyr and nicosulfuron (ALS inhibitors) clodinafop and haloxyfop (ACCase inhibitors). Each has a direct counterpart in the conesponding benzene series but, in these instances, the pyridine analog is invariably the superior herbicide. 

ACCase inhibitors Inhibition of acetyl CoA carboxylase (ACCase) Sethoxydim 0 46 46... 

---