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Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production
The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleT(JE). Herein, we desc...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235961/ https://www.ncbi.nlm.nih.gov/pubmed/37216508 http://dx.doi.org/10.1073/pnas.2221483120 |
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author | Rade, Leticia L. Generoso, Wesley C. Das, Suman Souza, Amanda S. Silveira, Rodrigo L. Avila, Mayara C. Vieira, Plinio S. Miyamoto, Renan Y. Lima, Ana B. B. Aricetti, Juliana A. de Melo, Ricardo R. Milan, Natalia Persinoti, Gabriela F. Bonomi, Antonio M. F. L. J. Murakami, Mario T. Makris, Thomas M. Zanphorlin, Leticia M. |
author_facet | Rade, Leticia L. Generoso, Wesley C. Das, Suman Souza, Amanda S. Silveira, Rodrigo L. Avila, Mayara C. Vieira, Plinio S. Miyamoto, Renan Y. Lima, Ana B. B. Aricetti, Juliana A. de Melo, Ricardo R. Milan, Natalia Persinoti, Gabriela F. Bonomi, Antonio M. F. L. J. Murakami, Mario T. Makris, Thomas M. Zanphorlin, Leticia M. |
author_sort | Rade, Leticia L. |
collection | PubMed |
description | The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleT(JE). Herein, we describe OleTP(RN), a poly-unsaturated alkene-producing decarboxylase that outrivals the functional properties of the model enzyme and exploits a distinct molecular mechanism for substrate binding and chemoselectivity. In addition to the high conversion rates into alkenes from a broad range of saturated FAs without dependence on high salt concentrations, OleTP(RN) can also efficiently produce alkenes from unsaturated (oleic and linoleic) acids, the most abundant FAs found in nature. OleTP(RN) performs carbon–carbon cleavage by a catalytic itinerary that involves hydrogen-atom transfer by the heme-ferryl intermediate Compound I and features a hydrophobic cradle at the distal region of the substrate-binding pocket, not found in OleT(JE), which is proposed to play a role in the productive binding of long-chain FAs and favors the rapid release of products from the metabolism of short-chain FAs. Moreover, it is shown that the dimeric configuration of OleTP(RN) is involved in the stabilization of the A-A’ helical motif, a second-coordination sphere of the substrate, which contributes to the proper accommodation of the aliphatic tail in the distal and medial active-site pocket. These findings provide an alternative molecular mechanism for alkene production by P450 peroxygenases, creating new opportunities for biological production of renewable hydrocarbons. |
format | Online Article Text |
id | pubmed-10235961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-102359612023-11-22 Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production Rade, Leticia L. Generoso, Wesley C. Das, Suman Souza, Amanda S. Silveira, Rodrigo L. Avila, Mayara C. Vieira, Plinio S. Miyamoto, Renan Y. Lima, Ana B. B. Aricetti, Juliana A. de Melo, Ricardo R. Milan, Natalia Persinoti, Gabriela F. Bonomi, Antonio M. F. L. J. Murakami, Mario T. Makris, Thomas M. Zanphorlin, Leticia M. Proc Natl Acad Sci U S A Biological Sciences The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleT(JE). Herein, we describe OleTP(RN), a poly-unsaturated alkene-producing decarboxylase that outrivals the functional properties of the model enzyme and exploits a distinct molecular mechanism for substrate binding and chemoselectivity. In addition to the high conversion rates into alkenes from a broad range of saturated FAs without dependence on high salt concentrations, OleTP(RN) can also efficiently produce alkenes from unsaturated (oleic and linoleic) acids, the most abundant FAs found in nature. OleTP(RN) performs carbon–carbon cleavage by a catalytic itinerary that involves hydrogen-atom transfer by the heme-ferryl intermediate Compound I and features a hydrophobic cradle at the distal region of the substrate-binding pocket, not found in OleT(JE), which is proposed to play a role in the productive binding of long-chain FAs and favors the rapid release of products from the metabolism of short-chain FAs. Moreover, it is shown that the dimeric configuration of OleTP(RN) is involved in the stabilization of the A-A’ helical motif, a second-coordination sphere of the substrate, which contributes to the proper accommodation of the aliphatic tail in the distal and medial active-site pocket. These findings provide an alternative molecular mechanism for alkene production by P450 peroxygenases, creating new opportunities for biological production of renewable hydrocarbons. National Academy of Sciences 2023-05-22 2023-05-30 /pmc/articles/PMC10235961/ /pubmed/37216508 http://dx.doi.org/10.1073/pnas.2221483120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Rade, Leticia L. Generoso, Wesley C. Das, Suman Souza, Amanda S. Silveira, Rodrigo L. Avila, Mayara C. Vieira, Plinio S. Miyamoto, Renan Y. Lima, Ana B. B. Aricetti, Juliana A. de Melo, Ricardo R. Milan, Natalia Persinoti, Gabriela F. Bonomi, Antonio M. F. L. J. Murakami, Mario T. Makris, Thomas M. Zanphorlin, Leticia M. Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title | Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title_full | Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title_fullStr | Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title_full_unstemmed | Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title_short | Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
title_sort | dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235961/ https://www.ncbi.nlm.nih.gov/pubmed/37216508 http://dx.doi.org/10.1073/pnas.2221483120 |
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