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Chemical genetics uncovers novel inhibitors of lignification, including p-iodobenzoic acid targeting CINNAMATE-4-HYDROXYLASE

(2016) PLANT PHYSIOLOGY. 172(1). p.198-220
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Abstract
Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization.
Keywords
LIGNIN BIOSYNTHESIS PERTURBATIONS, SUCROSE-SPECIFIC INDUCTION, ARABIDOPSIS-THALIANA, PATHWAY, BIOLOGY, SACCHARIFICATION, 4-HYDROXYLASE, ANTHOCYANINS, MOLECULES, RESPONSES

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Chicago
Van de Wouwer, Dorien, Ruben Vanholme, Raphael Decou, Geert Goeminne, Dominique Audenaert, Long Nguyen, René Höfer, Edouard Pesquet, Bartel Vanholme, and Wout Boerjan. 2016. “Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including P-iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.” Plant Physiology 172 (1): 198–220.
APA
Van de Wouwer, D., Vanholme, R., Decou, R., Goeminne, G., Audenaert, D., Nguyen, L., Höfer, R., et al. (2016). Chemical genetics uncovers novel inhibitors of lignification, including p-iodobenzoic acid targeting CINNAMATE-4-HYDROXYLASE. PLANT PHYSIOLOGY, 172(1), 198–220.
Vancouver
1.
Van de Wouwer D, Vanholme R, Decou R, Goeminne G, Audenaert D, Nguyen L, et al. Chemical genetics uncovers novel inhibitors of lignification, including p-iodobenzoic acid targeting CINNAMATE-4-HYDROXYLASE. PLANT PHYSIOLOGY. 2016;172(1):198–220.
MLA
Van de Wouwer, Dorien, Ruben Vanholme, Raphael Decou, et al. “Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including P-iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.” PLANT PHYSIOLOGY 172.1 (2016): 198–220. Print.
@article{8500668,
  abstract     = {Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization.},
  author       = {Van de Wouwer, Dorien and Vanholme, Ruben and Decou, Raphael and Goeminne, Geert and Audenaert, Dominique and Nguyen, Long and H{\"o}fer, Ren{\'e} and Pesquet, Edouard and Vanholme, Bartel and Boerjan, Wout},
  issn         = {0032-0889},
  journal      = {PLANT PHYSIOLOGY},
  keyword      = {LIGNIN BIOSYNTHESIS PERTURBATIONS,SUCROSE-SPECIFIC INDUCTION,ARABIDOPSIS-THALIANA,PATHWAY,BIOLOGY,SACCHARIFICATION,4-HYDROXYLASE,ANTHOCYANINS,MOLECULES,RESPONSES},
  language     = {eng},
  number       = {1},
  pages        = {198--220},
  title        = {Chemical genetics uncovers novel inhibitors of lignification, including p-iodobenzoic acid targeting CINNAMATE-4-HYDROXYLASE},
  url          = {http://dx.doi.org/10.1104/pp.16.00430},
  volume       = {172},
  year         = {2016},
}

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