How To Break the Janus Effect of H <sub>2</sub> O <sub>2</sub> in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes

Journal article (2019)

Authors

Ze Xin Zhao South China University of Technology
Dongming Lan South China University of Technology
Xiyu Tan South China University of Technology
F. Hollmann BT/Biocatalysis - AS
Uwe T. Bornscheuer Greifswald University
Bo Yang South China University of Technology
Yonghua Wang South China University of Technology
Research Group
BT/Biocatalysis (AS) (TU Delft)
Copyright: © 2019 Ze Xin Zhao, Dongming Lan, Xiyu Tan, F. Hollmann, Uwe T. Bornscheuer, Bo Yang, Yonghua Wang
DOI: https://doi.org/10.1021/acscatal.8b04948
Lipase Epoxidation H O Inactivation Multiscale MD QM/MM MD
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Published Date

2019

Language

English

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Faculty

Applied Sciences

Department

BT/Biotechnologie

Research Group

BT/Biocatalysis

Abstract


H
2
O
2
, is an attractive oxidant for synthetic chemistry, especially if activated as percarboxylic acid. H
2
O
2
, however, is also a potent inactivator of enzymes. Protein engineering efforts to improve enzyme resistance against H
2
O
2
in the past have mostly focused on tedious probabilistic directed evolution approaches. Here we demonstrate that a rational approach combining multiscale MD simulations and Born-Oppenheimer ab initio QM/MM MD simulations is an efficient approach to rapidly identify improved enzyme variants. Thus, the lipase from Penicillium camembertii was redesigned with a single mutation (I260R), leading to drastic improvements in H
2
O
2
resistance while maintaining the catalytic activity. Also the extension of this methodology to other enzymes is demonstrated.