How To Break the Janus Effect of H 2 O 2

Title

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

 Author

Zhao, Ze Xin (South China University of Technology)
Lan, Dongming (South China University of Technology)
Tan, Xiyu (South China University of Technology)
Hollmann, F. (TU Delft BT/Biocatalysis) ORCID 0000-0003-4821-756X
Bornscheuer, Uwe T. (Greifswald University)
Yang, Bo (South China University of Technology)
Wang, Yonghua (South China University of Technology)

Date

2019

 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.


Subject

epoxidation
H O
inactivation
lipase
multiscale MD
QM/MM MD

 To reference this document use:

http://resolver.tudelft.nl/uuid:0475d555-416d-4feb-97fb-066c951c6c5a

 DOI

https://doi.org/10.1021/acscatal.8b04948

 Embargo date

2019-08-28

 ISSN

2155-5435

 Source

ACS Catalysis, 9 (4), 2916-2921

 Bibliographical note

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.

 Part of collection

Institutional Repository

 Document type

journal article

 Rights

© 2019 Ze Xin Zhao, Dongming Lan, Xiyu Tan, F. Hollmann, Uwe T. Bornscheuer, Bo Yang, Yonghua Wang
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