An Artificial Heme Enzyme for Cyclopropanation Reactions

Lara Villarino; Kathryn E. Splan; Eswar Reddem; Lur Alonso-Cotchico; Cora Gutiérrez de Souza; Agustí Lledós; Jean Didier Maréchal; Andy Mark W.H. Thunnissen; Gerard Roelfes

doi:10.1002/anie.201802946

An Artificial Heme Enzyme for Cyclopropanation Reactions

Lara Villarino, Kathryn E. Splan, Eswar Reddem, Lur Alonso-Cotchico, Cora Gutiérrez de Souza, Agustí Lledós, Jean Didier Maréchal, Andy Mark W.H. Thunnissen, Gerard Roelfes

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

51 Citations (Scopus)

Abstract

© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.

Original language	English
Pages (from-to)	7785-7789
Journal	Angewandte Chemie - International Edition
Volume	57
Issue number	26
DOIs	https://doi.org/10.1002/anie.201802946
Publication status	Published - 25 Jun 2018

Keywords

artificial metalloenzymes
biocatalysis
carbenes
enzyme design
heme enzymes

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10.1002/anie.201802946

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title = "An Artificial Heme Enzyme for Cyclopropanation Reactions",

abstract = "{\textcopyright} 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.",

keywords = "artificial metalloenzymes, biocatalysis, carbenes, enzyme design, heme enzymes",

author = "Lara Villarino and Splan, {Kathryn E.} and Eswar Reddem and Lur Alonso-Cotchico and {Guti{\'e}rrez de Souza}, Cora and Agust{\'i} Lled{\'o}s and Mar{\'e}chal, {Jean Didier} and Thunnissen, {Andy Mark W.H.} and Gerard Roelfes",

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month = jun,

day = "25",

doi = "10.1002/anie.201802946",

language = "English",

volume = "57",

pages = "7785--7789",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

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An Artificial Heme Enzyme for Cyclopropanation Reactions. / Villarino, Lara; Splan, Kathryn E.; Reddem, Eswar; Alonso-Cotchico, Lur; Gutiérrez de Souza, Cora; Lledós, Agustí ; Maréchal, Jean Didier; Thunnissen, Andy Mark W.H.; Roelfes, Gerard.

In: Angewandte Chemie - International Edition, Vol. 57, No. 26, 25.06.2018, p. 7785-7789.

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

TY - JOUR

T1 - An Artificial Heme Enzyme for Cyclopropanation Reactions

AU - Villarino, Lara

AU - Splan, Kathryn E.

AU - Reddem, Eswar

AU - Alonso-Cotchico, Lur

AU - Gutiérrez de Souza, Cora

AU - Lledós, Agustí

AU - Maréchal, Jean Didier

AU - Thunnissen, Andy Mark W.H.

AU - Roelfes, Gerard

PY - 2018/6/25

Y1 - 2018/6/25

N2 - © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.

AB - © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.

KW - artificial metalloenzymes

KW - biocatalysis

KW - carbenes

KW - enzyme design

KW - heme enzymes

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DO - 10.1002/anie.201802946

M3 - Article

VL - 57

SP - 7785

EP - 7789

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

SN - 1433-7851

IS - 26

ER -

An Artificial Heme Enzyme for Cyclopropanation Reactions

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Keywords

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