Redox Engineering of Myoglobin by Cofactor Substitution to Enhance Cyclopropanation Reactivity

Kagawa, Yoshiyuki; Oohora, Koji; Himiyama, Tomoki et al.

Angewandte Chemie - International Edition, 2024

Number of Access:43（2025-04-28 15:11 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97611

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Title
Redox Engineering of Myoglobin by Cofactor Substitution to Enhance Cyclopropanation Reactivity
Creator
CreatorName
Kagawa, Yoshiyuki
NRID
1000010631202 1000010631202
ORCID
0000-0003-1155-6824 0000-0003-1155-6824
researchmap permalink
Oohora Oohora
Scopus Author ID
57200199412 57200199412
CreatorName
Oohora, Koji
NRID
1000090828310 1000090828310
CreatorName
Himiyama, Tomoki
NRID
1000060179190 1000060179190
CreatorName
Suzuki, Akihiro
NRID
1000020222226 1000020222226
ORCID
0000-0002-2215-935X 0000-0002-2215-935X
researchmap permalink
20190602_Sun 20190602_Sun
Scopus Author ID
55735983400 55735983400
CreatorName
Hayashi, Takashi
Subject
alkenes
artificial metalloenzymes
carbenes
cyclopropanation
reconstituted myoglobin
Description
Kagawa Y., Oohora K., Himiyama T., et al. Redox Engineering of Myoglobin by Cofactor Substitution to Enhance Cyclopropanation Reactivity. Angewandte Chemie - International Edition, (2024); https://doi.org/10.1002/anie.202403485.
Abstract
Design of metal cofactor ligands is essential for controlling the reactivity of metalloenzymes. We investigated a carbene transfer reaction catalyzed by myoglobins containing iron porphyrin cofactors with one and two trifluoromethyl groups at peripheral sites (FePorCF₃ and FePor(CF₃)₂, respectively), native heme and iron porphycene (FePc). These four myoglobins show a wide range of Fe(II)/Fe(III) redox potentials in the protein of +147 mV, +87 mV, +42 mV and −198 mV vs. NHE, respectively. Myoglobin reconstituted with FePor(CF₃)₂ has a more positive potential, which enhances the reactivity of a carbene intermediate with alkenes, and demonstrates superior cyclopropanation of inert alkenes, such as aliphatic and internal alkenes. In contrast, engineered myoglobin reconstituted with FePc has a more negative redox potential, which accelerates the formation of the intermediate, but has low reactivity for inert alkenes. Mechanistic studies indicate that myoglobin with FePor(CF₃)₂ generates an undetectable active intermediate with a radical character. In contrast, this reaction catalyzed by myoglobin with FePc includes a detectable iron–carbene species with electrophilic character. This finding highlights the importance of redox-focused design of the iron porphyrinoid cofactor in hemoproteins to tune the reactivity of the carbene transfer reaction.
Publisher
John Wiley and Sons Inc
Source Title
Angewandte Chemie - International Edition
Date of Issued
2024-07-04
Language
English
Handle URL
https://hdl.handle.net/11094/97611
PISSN
14337851
eISSN
15213773
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1002/anie.202403485
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article