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Simulations moléculaires appliquées à l'acétylation de flavonoïdes catalysée par des lipases : influence des structures de la lipase e du flavonoïde sur la régiosélectivité de la bioconversion

Abstract : Flavonoids are plant-produced polyhydroxylated compounds, well-known for their beneficial health effects. In order to obtain more stable and soluble derivatives for incorporation in hydrophobic formulations without damaging the biological activities of the native molecules, a solution consists to perform a regioselective acylation of these molecules. This can be accomplished by using lipase biocatalysts, in organic media. Several experimental studies dealing with such processes are available, but none of them give any explanation, at the molecular level, for the regioselectivity of such reactions. This study aimed to apply different molecular modelling tools in order to better understand, at the molecular level, the selectivity properties of the acetylation of three flavonoids (quercetin and its glycosylated derivatives isoquercitrin and rutin), by using the lipases CALB and PCL. Firstly, docking simulations were applied, in order to obtain the most probable positions and orientations of the flavonoids in the cavities of acetylated lipases. Then, molecular dynamics simulations were performed, aiming to study the structural stability of the complexes upon a period of time and specially the stability of the enzyme-substrates interactions. Finally, quantum chemical simulations (DFT) were applied to evaluate the chemical reactivity of the flavonoids as docked in the complexes. The trends observed during the simulations were well correlated with previous experimental results on the acetylation reaction of these flavonoids. Overall, the results showed that the selectivity in such reactions depends upon the substrates (flavonoid and acetate) orientations in the enzyme catalytic cavity, the intermolecular interactions that stabilize these substrates and the intrinsic chemical reactivity of the flavonoids OH groups reaching the catalytic residues.
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https://tel.archives-ouvertes.fr/tel-00452422
Contributor : Eduardo Basilio de Oliveira <>
Submitted on : Tuesday, February 16, 2010 - 5:09:03 PM
Last modification on : Thursday, January 7, 2021 - 3:39:10 PM
Long-term archiving on: : Friday, June 18, 2010 - 6:49:32 PM

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  • HAL Id : tel-00452422, version 1

Citation

Eduardo Basilio de Oliveira. Simulations moléculaires appliquées à l'acétylation de flavonoïdes catalysée par des lipases : influence des structures de la lipase e du flavonoïde sur la régiosélectivité de la bioconversion. Autre. Institut National Polytechnique de Lorraine - INPL, 2009. Français. ⟨tel-00452422⟩

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