16.4 Herbicides that Inhibit ALS

Herbicides that inhibit the production of the branched chain amino acids valine, leucine and isoleucine are used for total vegetation management and selective weed control in a wide variety of crops.  There are currently five different chemical families that share this MOA.  Research suggests that these herbicides are non-competitive inhibitors, meaning that the herbicide does not compete with plant’s substrates for binding to ALS.  Instead, these herbicides bind to some area away from the active site of ALS and this changes the 3D configuration of ALS reducing its affinity for its normal substrates.

Before the development of glyphosate-tolerance crop technology, branched chain amino acid inhibitors were the mainstay for several major row crops.  While this is still an important herbicide MOA, the major increase in herbicide resistance weeds since 1980 has been the direct result of selection pressure from these herbicides.  There are currently more weed species resistant to branched chain amino acid inhibitors than any other herbicide MOA (49 in the US).

The discovery of herbicides that inhibit the production of the branched chain amino acids leucine, isoleucine and valine was a major break-through in weed control technology.  Dupont (now part of Corteva Agriscience) commercialized the first sulfonylurea (SU) herbicide, chlorosulfuron, in the early 1980s followed shortly by American Cyanamid’s (now part of BASF) introduction of the first imidazolinone (IMI) for soybeans, imazaquin.  These  new herbicide families selectively controlled many important weed species at very low application rates.  They also had excellent crop safety over a wide range of crop growth stages with very low mammalian toxicity.  Since animals do not have ALS enzymes, the herbicide chemistries posed little or no risk to human health.

Chlorosulfuron was originally marketed as “Glean” for post emergent weed control in wheat.  Glean was first evaluated at several ounces per acre, but field evaluations quickly indicated that this herbicide was very effective at much lower use rates.* Glean provided excellent control of several weed species that were very difficult to control with auxinic  (2,4-D, MCPA, dicamba) or contact PSII inhibitors (bromoxynil) that were commonly used for broadleaf weed control in small grains.  One of the key weed species that drove the rapid adoption of this new technology was kochia (Kochia scoparia).  Initial kochia control with Glean was greater than 95%.  The rapid increase in ALS resistant kochia, which occurred a few years after Glean’s introduction, would foretell the weakness of ALS inhibitors.

*Always refer to product labels for appropriate application rates.

Here are time lapse videos of susceptible plant response to ALS Inhibitors:

For the full list of Ohio State University’s Weed Science herbicide time lapse videos, go to: https://www.youtube.com/playlist?list=PLrQLElJHkjuh65RjQZ8nWDBh0Da_MekB0

Sulfonylurea Herbicides (SU)

Initial field and laboratory studies with sulfonylurea herbicides revealed some remarkable attributes to this new chemistry.  Laboratory enzyme assays provided a good explanation for the extremely low use rates.  ALS I50 values (herbicide concentration required to reduce enzymatic activity by 50%) were in the low nM (10-9 molar) range.  Sulfonylurea herbicides are rapidly absorbed by roots and foliage, translocate in both xylem and phloem and have residual soil activity.  The residual soil activity was long enough to require significant plant back restrictions for sensitive broadleaf species, such as sugarbeets and potatoes.  Herbicide selectivity was found to be a function of metabolism rate; therefore, slight changes in chemical structure allowed for the development of herbicides that could be used selectively in previously sensitive broadleaf crops, like sugarbeet (triflusulfuron, UpBeet®) and potato (rimsulfuron, Matrix®).  Dependence on herbicide metabolism for selectivity means crop injury can occur under adverse weather conditions.

DuPont developed non-transgenic sulfonylurea-tolerant-soybean (STS) in the 1990s, marketed as Reliance STS or Synchrony STS varieties.  A POST application of chlorimuron and thifensulfuron was used to provide broad-spectrum weed control.

Sulfonylurea Family (SU)  – Group 2 (B)

Imidazolinone Herbicides (IMI)

The imidazolinone herbicides (IMIs) have many of the same characteristics as the SUs.  They are absorbed by both roots and shoots and have excellent translocation in both the xylem and phloem.  Like the SUs, there is significant residual soil activity to the point that there are 24 to 36 month plant back restrictions for some sensitive species.  IMI application rates are  higher than the SUs and this is consistent with the ALS I50 values that are in the lower µM (10-6 molar) range or 1000 times lower affinity for ALS than the SUs.   These herbicides are still very potent ALS inhibitors.  The primary markets for these herbicides are soybeans, alfalfa, peanuts and dry beans; however, imazathabenz  (Assert®, not currently registered for use in the United States) controls wild oat and several important broadleaf weeds in wheat and barley.  Imazapyr (Habitat®, Powerline®) is used for pipelines, rights-of-way, conifer release, brush and tree control.  Imazapyr  has an ideal combination of log Kow and pKa for long distance phloem transport.  This could explain why imazapyr is the only herbicide to control the invasive tree species, tamarix, when applied as a foliar treatment.

Like the SUs, IMI selectivity is based on rapid metabolism.  Legumes were found to have inherently high tolerance to the IMI’s due to rapid hydroxylation followed by glucose conjugation.  In the days before glyphosate-tolerant soybeans, the IMIs were the most important active ingredient in soybean production.  Alfalfa is also very tolerant to imazethapyr (Pursuit®) and imazamox (Raptor®).  This allowed for the rapid establishment of pure alfalfa stands without the need for a nurse crop and provided growers with excellent forage production the year of establishment.  Because rapid metabolism is responsible for selectivity adverse weather conditions can result in crop injury if herbicide metabolism is slowed by cool temperatures.

A series of IMI tolerant non-transgenic crops called Clearfield® have been developed by chemical mutagensis.  These included Clearfield corn, Clearfield canola, and Clearfield wheat.  In the case of Clearfield sunflowers the resistance gene was backcrossed into commercial sunflower varieties from IMI resistant wild sunflowers.

Imidazolinone Family (IMI)  – Group 2 (B)

Triazolopyrimidines

In the late 1990’s, Dow AgroSciences commercialized a new family of ALS inhibitors called the triazolopyrimidines.    These herbicides are readily translocated in the xylem and phloem, with better overall soil activity than foliar activity.  Selectivity is based on herbicide metabolism, for instance in corn the ½ life of flumetsulum is only 2 hours, while in sensitive weed species it can exceed 4 days.

Triazolopyrimidine Family  – Group 2 (B)

Pyrimidinylthiobenzoic acid

The pyrimidinylthio-benzoates are another herbicide family with an ALS target site. Pyrithiobac can be absorbed following both soil and foliar applications, but appears to translocate primarily in the phloem.

Sulfonylaminocarbonyl-triazoliniones

The final herbicide group that targets ALS belongs to a relatively new chemical family called the sulfonylaminocarbonyl-triazoliniones.  These herbicides can be absorbed by both roots and foliage and translocates in the xylem and phloem.  There is much flexibility in designing ALS targeted herbicides with very specific selectivity.  In the US, Olympus provides selective control of winter annual grasses primarily Bromussp. in winter wheat.  Monsanto has an SU that provides very similar selectivity called sulfosulfuron (Maverick®).

Summary of ALS Herbicide Injury Symptoms
In the early 1980’s growers associated good herbicide activity with rapid symptom development, but these new ALS inhibitors were very slow acting. If the weather was cool it could take 14 days to show good herbicide injury symptoms on susceptible weeds. One key symptom of ALS herbicides is that plants stop growing within hours of application. This kind of symptom is much more difficult to demonstrate unless treated and control plants are side by side.  One common feature of all ALS herbicides is that they need to have phloem mobility. Phloem mobility ensures that the herbicide will be translocated to root and shoot meristems. These are the sites of rapid growth, high demand for branched chain amino acids, high protein synthesis and maximum ALS activity. In fact ALS activity is almost undetectable in older leaves. Chlorosis of the shoot meristems is one of the most consistent symptoms of ALS injury.