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

Ze Xin Zhao, Dongming Lan, Xiyu Tan, Frank Hollmann, Uwe T. Bornscheuer, Bo Yang, Yonghua Wang*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)
88 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2916-2921
JournalACS Catalysis
Volume9
Issue number4
DOIs
Publication statusPublished - 2019

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.

Keywords

  • epoxidation
  • H O
  • inactivation
  • lipase
  • multiscale MD
  • QM/MM MD

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