Frontiers in Molecular Biosciences (May 2022)

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,
  • Xiao He,
  • John Z. H. Zhang,
  • John Z. H. Zhang,
  • John Z. H. Zhang,
  • Lujia Zhang,
  • Lujia Zhang

DOI
https://doi.org/10.3389/fmolb.2022.888721
Journal volume & issue
Vol. 9

Abstract

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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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