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Enzymatic Hydroxylation of Aliphatic C–H Bonds by a Mn/Fe Cofactor
[Image: see text] The aerobic oxidation of carbon–hydrogen (C–H) bonds in biology is currently known to be accomplished by a limited set of cofactors that typically include heme, nonheme iron, and copper. While manganese cofactors perform difficult oxidation reactions, including water oxidation with...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401708/ https://www.ncbi.nlm.nih.gov/pubmed/37471626 http://dx.doi.org/10.1021/jacs.3c03419 |
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author | Powell, Magan M. Rao, Guodong Britt, R. David Rittle, Jonathan |
author_facet | Powell, Magan M. Rao, Guodong Britt, R. David Rittle, Jonathan |
author_sort | Powell, Magan M. |
collection | PubMed |
description | [Image: see text] The aerobic oxidation of carbon–hydrogen (C–H) bonds in biology is currently known to be accomplished by a limited set of cofactors that typically include heme, nonheme iron, and copper. While manganese cofactors perform difficult oxidation reactions, including water oxidation within Photosystem II, they are generally not known to be used for C–H bond activation, and those that do catalyze this important reaction display limited intrinsic reactivity. Here we report that the 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis, AibH1H2, requires manganese to functionalize a strong, aliphatic C–H bond (BDE = 100 kcal/mol). Structural and spectroscopic studies of this enzyme reveal a redox-active, heterobimetallic manganese–iron active site at the locus of O(2) activation and substrate coordination. This result expands the known reactivity of biological manganese–iron cofactors, which was previously restricted to single-electron transfer or stoichiometric protein oxidation. Furthermore, the AibH1H2 cofactor is supported by a protein fold distinct from typical bimetallic oxygenases, and bioinformatic analyses identify related proteins abundant in microorganisms. This suggests that many uncharacterized monooxygenases may similarly require manganese to perform oxidative biochemical tasks. |
format | Online Article Text |
id | pubmed-10401708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-104017082023-08-05 Enzymatic Hydroxylation of Aliphatic C–H Bonds by a Mn/Fe Cofactor Powell, Magan M. Rao, Guodong Britt, R. David Rittle, Jonathan J Am Chem Soc [Image: see text] The aerobic oxidation of carbon–hydrogen (C–H) bonds in biology is currently known to be accomplished by a limited set of cofactors that typically include heme, nonheme iron, and copper. While manganese cofactors perform difficult oxidation reactions, including water oxidation within Photosystem II, they are generally not known to be used for C–H bond activation, and those that do catalyze this important reaction display limited intrinsic reactivity. Here we report that the 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis, AibH1H2, requires manganese to functionalize a strong, aliphatic C–H bond (BDE = 100 kcal/mol). Structural and spectroscopic studies of this enzyme reveal a redox-active, heterobimetallic manganese–iron active site at the locus of O(2) activation and substrate coordination. This result expands the known reactivity of biological manganese–iron cofactors, which was previously restricted to single-electron transfer or stoichiometric protein oxidation. Furthermore, the AibH1H2 cofactor is supported by a protein fold distinct from typical bimetallic oxygenases, and bioinformatic analyses identify related proteins abundant in microorganisms. This suggests that many uncharacterized monooxygenases may similarly require manganese to perform oxidative biochemical tasks. American Chemical Society 2023-07-20 /pmc/articles/PMC10401708/ /pubmed/37471626 http://dx.doi.org/10.1021/jacs.3c03419 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Powell, Magan M. Rao, Guodong Britt, R. David Rittle, Jonathan Enzymatic Hydroxylation of Aliphatic C–H Bonds by a Mn/Fe Cofactor |
title | Enzymatic Hydroxylation
of Aliphatic C–H Bonds
by a Mn/Fe Cofactor |
title_full | Enzymatic Hydroxylation
of Aliphatic C–H Bonds
by a Mn/Fe Cofactor |
title_fullStr | Enzymatic Hydroxylation
of Aliphatic C–H Bonds
by a Mn/Fe Cofactor |
title_full_unstemmed | Enzymatic Hydroxylation
of Aliphatic C–H Bonds
by a Mn/Fe Cofactor |
title_short | Enzymatic Hydroxylation
of Aliphatic C–H Bonds
by a Mn/Fe Cofactor |
title_sort | enzymatic hydroxylation
of aliphatic c–h bonds
by a mn/fe cofactor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401708/ https://www.ncbi.nlm.nih.gov/pubmed/37471626 http://dx.doi.org/10.1021/jacs.3c03419 |
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