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

doi:10.1021/acscatal.8b04948

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

BT/Biocatalysis

Research output: Contribution to journal › Article › Scientific › peer-review

18 Citations (Scopus)

106 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 language	English
Pages (from-to)	2916-2921
Journal	ACS Catalysis
Volume	9
Issue number	4
DOIs	https://doi.org/10.1021/acscatal.8b04948
Publication status	Published - 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

Access to Document

10.1021/acscatal.8b04948

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Cite this

Zhao, Z. X., Lan, D., Tan, X., Hollmann, F., Bornscheuer, U. T., Yang, B., & Wang, Y. (2019). How To Break the Janus Effect of H ₂ O ₂ in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes. ACS Catalysis, 9(4), 2916-2921. https://doi.org/10.1021/acscatal.8b04948

Zhao, Ze Xin ; Lan, Dongming ; Tan, Xiyu et al. / How To Break the Janus Effect of H ₂ O ₂ in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes. In: ACS Catalysis. 2019 ; Vol. 9, No. 4. pp. 2916-2921.

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

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. ",

keywords = "epoxidation, H O, inactivation, lipase, multiscale MD, QM/MM MD",

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Zhao, ZX, Lan, D, Tan, X, Hollmann, F, Bornscheuer, UT, Yang, B & Wang, Y 2019, 'How To Break the Janus Effect of H ₂ O ₂ in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes', ACS Catalysis, vol. 9, no. 4, pp. 2916-2921. https://doi.org/10.1021/acscatal.8b04948

How To Break the Janus Effect of H ₂ O ₂ in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes. / Zhao, Ze Xin; Lan, Dongming; Tan, Xiyu et al.
In: ACS Catalysis, Vol. 9, No. 4, 2019, p. 2916-2921.

Research output: Contribution to journal › Article › Scientific › peer-review

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AU - Bornscheuer, Uwe T.

AU - Yang, Bo

AU - Wang, Yonghua

N1 - 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.

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AB - 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.

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Zhao ZX, Lan D, Tan X, Hollmann F, Bornscheuer UT, Yang B et al. How To Break the Janus Effect of H ₂ O ₂ in Biocatalysis? Understanding Inactivation Mechanisms To Generate more Robust Enzymes. ACS Catalysis. 2019;9(4):2916-2921. doi: 10.1021/acscatal.8b04948