Physionomics and metabolomics—two key approaches in herbicidal mode of action discovery

Großmann, Klaus; Christiansen, Nicole; Looser, Ralf; Tresch, Stefan; Hutzler, Johannes; Pollmann, Stephan; Ehrhardt, Thomas

doi:10.1002/ps.2300

Cited by 38 publications

(42 citation statements)

References 36 publications

(58 reference statements)

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“…Such behavior is consistent with active (ATP-dependent) membrane glyphosate transport. It is anticipated that in vivo NMR studies of whole-plant tissue will continue to play an important role in understanding herbicide action in weeds and genetically modified crops (Dayan et al, 2010;Grossmann et al, 2012;Délye et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

In Vivo 31P-Nuclear Magnetic Resonance Studies of Glyphosate Uptake, Vacuolar Sequestration, and Tonoplast Pump Activity in Glyphosate-Resistant Horseweed

Ge¹,

d’Avignon²,

Ackerman

et al. 2014

Plant Physiology

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Horseweed (Conyza canadensis) is considered a significant glyphosate-resistant (GR) weed in agriculture, spreading to 21 states in the United States and now found globally on five continents. This laboratory previously reported rapid vacuolar sequestration of glyphosate as the mechanism of resistance in GR horseweed. The observation of vacuole sequestration is consistent with the existence of a tonoplast-bound transporter. 31 P-Nuclear magnetic resonance experiments performed in vivo with GR horseweed leaf tissue show that glyphosate entry into the plant cell (cytosolic compartment) is (1) first order in extracellular glyphosate concentration, independent of pH and dependent upon ATP; (2) competitively inhibited by alternative substrates (aminomethyl phosphonate [AMPA] and N-methyl glyphosate [NMG]), which themselves enter the plant cell; and (3) blocked by vanadate, a known inhibitor/blocker of ATP-dependent transporters. Vacuole sequestration of glyphosate is (1) first order in cytosolic glyphosate concentration and dependent upon ATP; (2) competitively inhibited by alternative substrates (AMPA and NMG), which themselves enter the plant vacuole; and (3) saturable.31 P-Nuclear magnetic resonance findings with GR horseweed are consistent with the active transport of glyphosate and alternative substrates (AMPA and NMG) across the plasma membrane and tonoplast in a manner characteristic of ATP-binding cassette transporters, similar to those that have been identified in mammalian cells.

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Section: Resultsmentioning

confidence: 99%

In Vivo 31P-Nuclear Magnetic Resonance Studies of Glyphosate Uptake, Vacuolar Sequestration, and Tonoplast Pump Activity in Glyphosate-Resistant Horseweed

Ge¹,

d’Avignon²,

Ackerman

et al. 2014

Plant Physiology

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“…Tissue culture tests as described by Gressel et al (1993) were also employed by a number of companies. Some companies have kept and improved such miniaturized assays until today, as published by Grossmann et al (2012). Several assays were incorporated into highthroughput screening systems that allow the screening of one million compounds per year and more (Kraehmer, 2012).…”

Section: Miniaturized Screening Assaysmentioning

confidence: 99%

“…It is highly questionable if all compounds controlling Lemna spp., Arabidopsis, and B. distachyon will, for example, automatically control herbicide-resistant Amaranthus spp. This is presumably why cells or tissues of target species have now found their way into physiological profiling assays (Grossmann et al, 2012).…”

Section: Glasshouse-to-field Transfermentioning

confidence: 99%

“…To achieve this goal, previously discovered but not commercialized targets might be reconsidered in the light of new technological advances in drug discovery in the last 20 years, such as fragment (ligand)-based drug design. Alternatively, hits from greenhouse screening might be subjected to MoA elucidation using state-of-the-art omics technologies (Grossmann et al, 2012;Tresch, 2013) in order to identify novel starting points for herbicide discovery.…”

Section: Moas and Herbicide Diversitymentioning

confidence: 99%

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Herbicides as Weed Control Agents: State of the Art: I. Weed Control Research and Safener Technology: The Path to Modern Agriculture

et al. 2014

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The purpose of modern industrial herbicides is to control weeds. The species of weeds that plague crops today are a consequence of the historical past, being related to the history of the evolution of crops and farming practices. Chemical weed control began over a century ago with inorganic compounds and transitioned to the age of organic herbicides. Targeted herbicide research has created a steady stream of successful products. However, safeners have proven to be more difficult to find. Once found, the mode of action of the safener must be determined, partly to help in the discovery of further compounds within the same class. However, mounting regulatory and economic pressure has changed the industry completely, making it harder to find a successful herbicide. Herbicide resistance has also become a major problem, increasing the difficulty of controlling weeds. As a result, the development of new molecules has become a rare event today.

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“…The study of small-molecule metabolite profiles, generally referred to as metabolomics (Kamp et al, 2012), and gene expression profiling (Eckes and Busch, 2012) are valuable tools in this context. Alternatively, new herbicidal leads also may arise from the combination of wholeplant screening with physiological investigations, recently defined as physionomics (Grossmann et al, 2012). All these approaches are covered under the general concept of systems biology, which is a more holistic approach to biological research (Kitano, 2002).…”

Section: New Discovery Approachesmentioning

confidence: 99%

Herbicides as Weed Control Agents: State of the Art: II. Recent Achievements

et al. 2014

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In response to changing market dynamics, the discovery of new herbicides has declined significantly over the past few decades and has only seen a modest upsurge in recent years. Nevertheless, the few introductions have proven to be interesting and have brought useful innovation to the market. In addition, herbicide-tolerant or herbicide-resistant crop technologies have allowed the use of existing nonselective herbicides to be extended into crops. An increasing and now major challenge is being posed by the inexorable increase in biotypes of weeds that are resistant to herbicides. This problem is now at a level that threatens future agricultural productivity and needs to be better understood. If herbicides are to remain sustainable, then it is a must that we adopt diversity in crop rotation and herbicide use as well as increase the use of nonchemical measures to control weeds. Nevertheless, despite the difficulties posed by resistant weeds and increased regulatory hurdles, new screening tools promise to provide an upsurge of potential herbicide leads. Our industry urgently needs to supply agriculture with new, effective resistance-breaking herbicides along with strategies to sustain their utility.Only a few companies are significantly pursuing herbicide discovery in the 21st century. Most of these have combined seed and traits businesses, since fees for traits constitute a considerable part of the income of agrochemical companies today. In concert with a review of the historical perspectives of herbicide research (Kraehmer et al., 2014), we provide here a short description of the current major research activities within the remaining 21st century agrochemical companies. After an overview of the chemicals that have entered the market in the 21st century, we provide a brief summary of the current nature of the weed-resistant herbicide problem. We then go on to summarize breedingassisted and transgenic approaches toward the improvement of crop selectivity through the delivery of so-called herbicide-tolerant (HT) or herbicide-resistant crops, and conclude with a discussion of the new herbicide discovery screening tools that have been employed since the year 2000 and prospects for the future. MAJOR CHEMICAL TRENDS AFTER 2000Several new compounds have entered the herbicide market in recent years. Although not representing new modes of action (MoAs), they have increased the number of tools available for farmers to use to control weeds. Even in known and older herbicidal classes, new, interesting, and marketable molecules have been discovered. For example, and perhaps surprising given the relative age of the class of herbicides, new (after 2000) acetolactate synthase (ALS) inhibitors have provided solutions for farmers that can be regarded as real innovations. One of them is mesosulfuron-methyl (Fig. 1), a sulfonylurea herbicide that, when combined with iodosulfuron-methyl sodium, has broad-spectrum postemergence grass weed control at dose rates of 4.5 to 15 g active ingredient (a.i.) ha 21 (Safferling, 2005). Another ...

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Physionomics and metabolomics—two key approaches in herbicidal mode of action discovery

Abstract: The value of this cascade strategy is exemplified by new herbicides with MoAs in plastoquinone, auxin or very-long-chain fatty acid synthesis.

Cited by 38 publications

References 36 publications

In Vivo 31P-Nuclear Magnetic Resonance Studies of Glyphosate Uptake, Vacuolar Sequestration, and Tonoplast Pump Activity in Glyphosate-Resistant Horseweed

In Vivo 31P-Nuclear Magnetic Resonance Studies of Glyphosate Uptake, Vacuolar Sequestration, and Tonoplast Pump Activity in Glyphosate-Resistant Horseweed

Herbicides as Weed Control Agents: State of the Art: I. Weed Control Research and Safener Technology: The Path to Modern Agriculture

Herbicides as Weed Control Agents: State of the Art: II. Recent Achievements

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