Rational Design of P450 aMOx for Improving Anti-Markovnikov Selectivity Based on the “Butterfly” Model

Aromatic aldehydes are important industrial raw materials mainly synthesized by anti-Markovnikov (AM) oxidation of corresponding aromatic olefins. The AM product selectivity remains a big challenge. P450 aMOx is the first reported enzyme that could catalyze AM oxidation of aromatic olefins. Here, we...

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Detalles Bibliográficos
Autores principales: Pan, Yue, Bao, Jinxiao, Zhang, Xingyi, Ni, Hui, Zhao, Yue, Zhi, Fengdong, Fang, Bohuan, He, Xiao, Zhang, John Z. H., Zhang, Lujia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Molecular Biosciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168652/
https://www.ncbi.nlm.nih.gov/pubmed/35677881
http://dx.doi.org/10.3389/fmolb.2022.888721
Descripción
Sumario:Aromatic aldehydes are important industrial raw materials mainly synthesized by anti-Markovnikov (AM) oxidation of corresponding aromatic olefins. The AM product selectivity remains a big challenge. P450 aMOx is the first reported enzyme that could catalyze AM oxidation of aromatic olefins. Here, we reported a rational design strategy based on the “butterfly” model of the active site of P450 aMOx. Constrained molecular dynamic simulations and a binding energy analysis of key residuals combined with an experimental alanine scan were applied. As a result, the mutant A275G showed high AM selectivity of >99%. The results also proved that the “butterfly” model is an effective design strategy for enzymes.

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