Modification de la composition en molécules pharmaceutiques (furocoumarines) de la Rue officinale (Ruta graveolens) par transformation génétique

Abstract : Furocoumarins are plant secondary metabolites that are used in cancer treatrnent. Ruta graveolens L. produces high amount of these molecules, whose chemical synthesis are very expansive. We decided to deepen our knowledge on the furocoumarins biosynthesis pathway and to try to improve their synthesis (metabolic engineering approach). We established the first Agrobacterium-mediated transformation protocol of Ruta graveolens L. Optimisation allowed us to settle an efficient method. The transformation rate is about 10 %. T0 transformants can be soil- grown 4 months after genetic transformation. Molecular tools have been developped in order to control the genetic transformation. We used this transformation method to improve our knowledge on furocoumarins biosynthesis. Introduction of CYP73A32, encoding cinnamate-4-hydroxylase in Ruta graveolens L. results in a qualitive modification of furocoumarins biosynthesis. The transformants have a lower amount of psoralen and higher ones for bergapten and xanthotoxin. One transformant, named K38, displays a particular phenotype (dwarf, very branched), and its furocoumarin profile is quantita.-ely and qualitatively modified (75 folds lower, and a ratio bergapten/xanthotoxin 3 folds higher than those in other plants). This work demonstrates that it is possible to modify the synthesis of furocoumarins.
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Theses
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http://docnum.univ-lorraine.fr/prive/INPL_T_2004_LIEVRE_K.pdf
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https://hal.univ-lorraine.fr/tel-01750045
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Submitted on : Thursday, March 29, 2018 - 12:36:35 PM
Last modification on : Wednesday, July 25, 2018 - 1:23:43 AM

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Karine Lièvre. Modification de la composition en molécules pharmaceutiques (furocoumarines) de la Rue officinale (Ruta graveolens) par transformation génétique. Sciences agricoles. Institut National Polytechnique de Lorraine, 2004. Français. ⟨NNT : 2004INPL003N⟩. ⟨tel-01750045⟩

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