Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.
Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.
Biochemical Plant Physiology, Heinrich Heine University Düsseldorf and Bioeconomy Science Center (BioSC), Universitätsstr.1, 40225 Düsseldorf, Germany.
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Nguyen
Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf and Bioeconomy Science Center (BioSC), Universitätsstr.1, 40225 Düsseldorf, Germany.
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Erlenkamp
Institute of Bio- and Geosciences, IBG-2: Plant Sciences, Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
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Jäck
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
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Küberl
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
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Bott
Institute of Bio- and Geosciences, IBG-2: Plant Sciences, Forschungszentrum Jülich and Bioeconomy Science Center (BioSC), Wilhelm-Johnen-Straße, 52425 Jülich, Germany.
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Fiorani
Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf and Bioeconomy Science Center (BioSC), Universitätsstr.1, 40225 Düsseldorf, Germany.
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Gohlke
Biochemical Plant Physiology, Heinrich Heine University Düsseldorf and Bioeconomy Science Center (BioSC), Universitätsstr.1, 40225 Düsseldorf, Germany.
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Groth
D027721:Amaranthus / Q000187:drug effects* / Q000254:growth & development*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D029688:Brassica napus / Q000187:drug effects / Q000254:growth & development; D047188:Chalcones / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006540:Herbicides / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D010730:Phosphoenolpyruvate Carboxylase / Q000037:antagonists & inhibitors*
D047188:Chalcones; D004791:Enzyme Inhibitors; D006540:Herbicides; D010730:Phosphoenolpyruvate Carboxylase