**4. Weed resistance to herbicides ACC‐ase inhibitors**

Herbicides acetyl‐CoenzymeA carboxylase (ACC‐ase) inhibitors are aryloxyphenoxy‐ propionates (APPs/FOPs), cyclohexanediones (CHDs/DIMs) and phenylpyrazoline. The first herbicide ACC‐ase inhibitors commercialized in 1975 [104]. They are used as foliar herbicides to control monocot weed species in dicot crops and some of them even in cere‐ als or in rice. The mode of action of these herbicides is inhibition of fatty acid biosynthesis through blocking of the acetyl‐CoenzymeA carboxylase [105]. Inhibition of lipid biosyn‐ thesis can explain the reduction of growth, increase in permeability of membrane and the ultrastructural effects commonly observed. In living organisms, ACC‐ase exists in two dif‐ ferent types: multi‐subunit type and multi‐functional type with 17–51 kDa (prokaryote) and 220–280 kDa (eukaryote) in size, respectively [106]. In dicot plants, the enzyme is struc‐ turally distinguished from the enzyme of monocots which contains four regions (biotin carboxylase, biotin carboxy carrier protein, carboxyl‐transferase α and β), while in dicots, they are encoded on separate proteins.

The frequent use of FOPs and DIMs has resulted in the development of resistance to ACC‐ase inhibitors in some monocot species in many countries in the world. Currently, 48 weed spe‐ cies have evolved resistance to these herbicides [7]. By decades, dynamics of the confirmation of the first cases of resistant weed species to the ACC‐ase can be seen in **Table 2**. Generally, mechanisms of resistance to ACC‐inhibiting herbicides can be divided in two categories: ACC‐related and metabolism‐based. Target‐site resistance to ACC‐ase inhibitors due to the herbicides binding to the carboxyl‐transferase region within the ACC‐ase enzyme results in amino acid substitution in that region (**Figure 4**) [107, 108]. Weed species or genera with high affinity of target‐site ACC‐ase resistance are *A. myosuroides*, *Avena* sp., *Bechmannia syzigachne*, *E. crus‐galli*, *Lolium* sp., etc. Most commonly amino acid substitution such as Ile‐1781‐Leu, Trp‐1999‐Cys, Trp‐2027‐Cys, Ile‐2041‐Asn, Asp‐2078‐Gly, Cys‐2088‐Arg, Gly‐2096‐Ser was confirmed in monocot resistant populations of weed species [109–116]. Amino acid substi‐ tutions such as Asp‐2078‐Gly and Cys‐2088‐Arg usually provide strong level of resistance to all ACC‐ase (FOPs, DIMs, pinoxaden) inhibitors [81]. Moreover, altered enzyme activity, gene expression and detoxification were very often included in weed resistance to ACC‐ase inhibiting herbicides (**Table 5**). Also, in some population of weed species such as *A. myo‐ suroides* [117], *E. crus‐galli* [118], *L. rigidum* [111] and *Lolium perenne* [85], target and non‐tar‐ get multiple‐resistance, which involves ACC‐ase and ALS inhibitors or ACC‐ase and EPSPS inhibitors, was confirmed.

The most different amino acid substitutions in α‐domain at position Pro‐197 have been linked in confirmed weed‐resistant species such as: *K. scoparia* (Pro‐197‐Ser/Thr/Leu/ Ala/Gln/Arg), *Descurainia sophia* (Pro‐197‐Ser/Thr/Leu/Ala/His/Tyr), *P. rhoeas* (Pro‐197‐ Ser/Thr/Leu/Ala/His/Arg), *L. rigidum* (Pro‐197‐Ser/Leu/Ala/Gln/Arg), *Apera spica‐venti* (Pro‐197‐Ser/Thr/Ala/Asn), etc. Also, the substitution of Trp‐574‐Leu confers resistance to several weed species (*A. retroflexus*, *C. iria*, *D. sophia*, *C. canadensis*, *K. scoparia*, *P. annua* etc.) and the levels of resistance are all high against SUs, IMIs and TPs (cross‐resistance) [29, 79–83]. Generally, the low number of confirmed weeds resistant to ALS inhibitors is due to altered enzyme activity, reduced translocation and detoxification. Additionally, many weed populations resistant to ALS inhibitors have developed multiple‐resistance to other chemical classes with different modes of action (e.g. auxinic herbicides, EPSPS inhibitors,

*Setaria viridis* (L.) Beauv. Ser‐653‐Asn/Thr/Ile, Gly‐654‐Asp Altered enzyme activity [97]

*Sorghum bicolor* (L.) Moench Altered enzyme activity [98, 99]

*Stellaria media* (L.) Vill. Pro‐197‐Gln, Trp‐574‐Leu Altered enzyme activity [101]

Trp‐574‐Leu

Trp‐574‐Leu

Amino acid substitution in weed‐resistant species to ALS inhibitors downloaded from HRAC [103].

**Table 4.** Confirmed mechanisms of resistance to herbicide ALS inhibitors in some weed species.

**Amino acid substitutions Other mechanisms of resistance**

Altered enzyme activity [102]

Herbicides acetyl‐CoenzymeA carboxylase (ACC‐ase) inhibitors are aryloxyphenoxy‐ propionates (APPs/FOPs), cyclohexanediones (CHDs/DIMs) and phenylpyrazoline. The first herbicide ACC‐ase inhibitors commercialized in 1975 [104]. They are used as foliar

ACC‐ase inhibitors) [31, 84, 85].

**Weed species Mechanism of resistance**

*Schoenoplectus mucronatus* (L.) Palla Pro‐197‐His, Trp‐574‐Leu

*Sinapis arvensis* L. Pro‐197‐Ser, Asp‐376‐Glu,

*Sisymbrium orientale* Torn. Pro‐197‐Ile, Trp‐574‐Leu *Solanum ptycanthum* Dunn Ala‐122‐Thr, Ala‐205‐Val

*Senecio vulgaris* L. Pro‐197‐Ser/Leu

16 Herbicide Resistance in Weeds and Crops

*Sonchus asper* (L.) Mill. Pro‐197‐Leu

*Thlaspi arvense* L. Pro‐197‐Leu

*Sorghum halepense* (L.) Pers. Trp‐574‐Leu [100]

*Xanthium strumarium* L. Ala‐122‐Thr, Ala‐205‐Val,

**4. Weed resistance to herbicides ACC‐ase inhibitors**

**Figure 4.** Single amino acid mutations in acetyl‐CoA carboxylase in monocot‐resistant weed populations (downloaded from Ref. [108]).


**Table 5.** Confirmed mechanisms of resistance to herbicide ACC‐ase inhibitors in some weed species.
