Print Email Facebook Twitter 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) 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 epoxidationH Oinactivationlipasemultiscale MDQM/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 Files PDF acscatal.8b04948.pdf 6.35 MB Close viewer /islandora/object/uuid:0475d555-416d-4feb-97fb-066c951c6c5a/datastream/OBJ/view