Chemical genetics: catalysing pathway exploration and new target discovery

Armstrong, Joshua I.

doi:10.1002/jsfa.2967

Cited by 5 publications

(2 citation statements)

References 35 publications

(37 reference statements)

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“…Chemical genetics, the systematic exploration of plant biological pathways with small molecule probes, is becoming increasingly popular (Armstrong 2007;Blackwell and Zhao 2003). Chemical genetics couples the diverse chemistry of nature and the large combinatorial libraries available to agrochemical industries with the strengths of molecular genetics to dissect signaling pathways in complex organisms, such as plants.…”

Section: Chemical Genetics To Probe Plant Biological Pathwaysmentioning

confidence: 99%

Herbicides as Probes in Plant Biology

Dayan

Duke

Großmann³

2010

Weed sci.

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Herbicides are small molecules that inhibit specific molecular target sites within plant biochemical pathways and/or physiological processes. Inhibition of these sites often has catastrophic consequences that are lethal to plants. The affinity of these compounds for their respective target sites makes them useful tools to study and dissect the intricacies of plant biochemical and physiological processes. For instance, elucidation of the photosynthetic electron transport chain was achieved in part by the use of herbicides, such as terbutryn and paraquat, which act on photosystem II and I, respectively, as physiological probes. Work stemming from the discovery of the binding site of PS II–inhibiting herbicides was ultimately awarded the Nobel Prize in 1988. Although not as prestigious as the seminal work on photosynthesis, our knowledge of many other plant processes expanded significantly through the ingenious use of inhibitors as molecular probes. Examples highlight the critical role played by herbicides in expanding our understanding of the fundamental aspects of the synthesis of porphyrins and the nonmevalonate pathway, the evolution of acetyl-coenzyme A carboxylase, cell wall physiology, the functions of microtubules and the cell cycle, the role of auxin and cyanide, the importance of subcellular protein targeting, and the development of selectable markers.

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Section: Chemical Genetics To Probe Plant Biological Pathwaysmentioning

confidence: 99%

Herbicides as Probes in Plant Biology

Dayan

Duke

Großmann³

2010

Weed sci.

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“…In the reverse chemical genetics approach, small molecules are identified that are active against known target proteins; they are then applied to a biological system to investigate protein function in vivo (28,29). This approach is complementary to conventional genetics since the small molecules can be applied easily to a broad range of species, their application can be controlled in dose, time, and space to provide detailed studies of biological functions, and individual proteins or whole protein classes may be targeted by varying the specificity of the small molecules.…”

mentioning

confidence: 99%

Selective Inhibition of Carotenoid Cleavage Dioxygenases

Sergeant

Fox

et al. 2009

Journal of Biological Chemistry

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Members of the carotenoid cleavage dioxygenase family catalyze the oxidative cleavage of carotenoids at various chain positions, leading to the formation of a wide range of apocarotenoid signaling molecules. To explore the functions of this diverse enzyme family, we have used a chemical genetic approach to design selective inhibitors for different classes of carotenoid cleavage dioxygenase. A set of 18 arylalkyl-hydroxamic acids was synthesized in which the distance between an iron-chelating hydroxamic acid and an aromatic ring was varied; these compounds were screened as inhibitors of four different enzyme classes, either in vitro or in vivo. Potent inhibitors were found that selectively inhibited enzymes that cleave carotenoids at the 9,10 position; 50% inhibition was achieved at submicromolar concentrations. Application of certain inhibitors at 100 M to Arabidopsis node explants or whole plants led to increased shoot branching, consistent with inhibition of 9,10-cleavage.

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Prospects and Challenges for Translating Emerging Insights in Plant Chemical Biology into New Agrochemicals

Walsh¹

2013

Plant Chemical Biology

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Chemical genetics: catalysing pathway exploration and new target discovery

Cited by 5 publications

References 35 publications

Herbicides as Probes in Plant Biology

Herbicides as Probes in Plant Biology

Selective Inhibition of Carotenoid Cleavage Dioxygenases

Prospects and Challenges for Translating Emerging Insights in Plant Chemical Biology into New Agrochemicals

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