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

Yue Pan; Jinxiao Bao; Xingyi Zhang; Hui Ni; Yue Zhao; Fengdong Zhi; Bohuan Fang; Xiao He; John Z.H. Zhang; Lujia Zhang

doi:10.3389/fmolb.2022.888721

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

Yue Pan, Jinxiao Bao, Xingyi Zhang, Hui Ni, Yue Zhao, Fengdong Zhi, Bohuan Fang, Xiao He^*, John Z.H. Zhang^*, Lujia Zhang^*

^*Corresponding author for this work

School of Chemistry and Molecular Engineering

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Article number	888721
Journal	Frontiers in Molecular Biosciences
Volume	9
DOIs	https://doi.org/10.3389/fmolb.2022.888721
State	Published - 23 May 2022

Keywords

anti-Markovnikov (AM) oxidation
experimental alanine scan
molecular dynamic simulations
product selectivity
rational design
“butterfly” model

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10.3389/fmolb.2022.888721

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@article{1eb2e545813b48edb22089379484ba7e,

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

abstract = "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.",

keywords = "anti-Markovnikov (AM) oxidation, experimental alanine scan, molecular dynamic simulations, product selectivity, rational design, “butterfly” model",

author = "Yue Pan and Jinxiao Bao and Xingyi Zhang and Hui Ni and Yue Zhao and Fengdong Zhi and Bohuan Fang and Xiao He and Zhang, \{John Z.H.\} and Lujia Zhang",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Pan, Bao, Zhang, Ni, Zhao, Zhi, Fang, He, Zhang and Zhang.",

year = "2022",

month = may,

day = "23",

doi = "10.3389/fmolb.2022.888721",

language = "英语",

volume = "9",

journal = "Frontiers in Molecular Biosciences",

issn = "2296-889X",

publisher = "Frontiers Media SA",

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TY - JOUR

T1 - Rational Design of P450 aMOx for Improving Anti-Markovnikov Selectivity Based on the “Butterfly” Model

AU - Pan, Yue

AU - Bao, Jinxiao

AU - Zhang, Xingyi

AU - Ni, Hui

AU - Zhao, Yue

AU - Zhi, Fengdong

AU - Fang, Bohuan

AU - He, Xiao

AU - Zhang, John Z.H.

AU - Zhang, Lujia

PY - 2022/5/23

Y1 - 2022/5/23

N2 - 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.

AB - 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.

KW - anti-Markovnikov (AM) oxidation

KW - experimental alanine scan

KW - molecular dynamic simulations

KW - product selectivity

KW - rational design

KW - “butterfly” model

UR - https://www.scopus.com/pages/publications/85131824729

U2 - 10.3389/fmolb.2022.888721

DO - 10.3389/fmolb.2022.888721

M3 - 文章

AN - SCOPUS:85131824729

SN - 2296-889X

VL - 9

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

M1 - 888721

ER -

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

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Keywords

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