Repurposing myoglobin into a carbene transferase for a [2,3]-sigmatropic Sommelet-Hauser rearrangement

International audience New-to-Nature biocatalysis has emerged as a promising tool in organic synthesis thanks to progress in protein engineering. Notably, hemeproteins have been evolved into robust catalysts for carbene and nitrene transfers and related sigmatropic rearrangements. In this work, we r...

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Bibliographic Details
Published in:Journal of Inorganic Biochemistry
Main Authors: Pujol, Manon, Degeilh, Lison, Sauty de Chalon, Thibault, Réglier, Marius, Simaan, A. Jalila, Decroos, Christophe
Other Authors: Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-18-CE07-0003,Abiozyme,Ingénierie de nouvelles métalloenzymes pour la catalyse abiologique(2018)
Format: Article in Journal/Newspaper
Language:English
Published: HAL CCSD 2024
Subjects:
artificial heme enzyme
sigmatropic rearrangement
carbene transfer
ylides
carbenoids
[CHIM.ORGA]Chemical Sciences/Organic chemistry
[CHIM.CATA]Chemical Sciences/Catalysis
Doyle
Sperm whale
Online Access:https://hal.science/hal-04668325
https://hal.science/hal-04668325/document
https://hal.science/hal-04668325/file/SommeletHauser_JInorgBiochem_R1.pdf
https://doi.org/10.1016/j.jinorgbio.2024.112688
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Summary:International audience New-to-Nature biocatalysis has emerged as a promising tool in organic synthesis thanks to progress in protein engineering. Notably, hemeproteins have been evolved into robust catalysts for carbene and nitrene transfers and related sigmatropic rearrangements. In this work, we report the first example of a [2,3]-sigmatropic Sommelet-Hauser rearrangement initiated by a carbene transfer of the sperm whale myoglobin mutant L29S,H64V,V68F that was previously reported to catalyze the mechanistically similar [2,3]-sigmatropic Doyle-Kirmse rearrangement. This repurposed heme enzyme catalyzes the Sommelet-Hauser rearrangement between ethyl diazoacetate and benzyl thioethers bearing strong electron-withdrawing substituents with good yields and enantiomeric excess. Optimized catalytic conditions in the absence of any reductant led to an increased asymmetric induction with up to 59% enantiomeric excess. This myoglobin mutant is therefore one of the few catalysts for the asymmetric Sommelet-Hauser rearrangement. This work broadens the scope of abiological reactions catalyzed by iron-carbene transferases with a new example of asymmetric sigmatropic rearrangement.

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