Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid

Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed geno...

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Autores principales: Isobe, Yosuke, Itagaki, Mai, Ito, Yuko, Naoe, Satoko, Kojima, Kotoe, Ikeguchi, Mitsunori, Arita, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962638/
https://www.ncbi.nlm.nih.gov/pubmed/29784972
http://dx.doi.org/10.1038/s41598-018-26325-4
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author Isobe, Yosuke
Itagaki, Mai
Ito, Yuko
Naoe, Satoko
Kojima, Kotoe
Ikeguchi, Mitsunori
Arita, Makoto
author_facet Isobe, Yosuke
Itagaki, Mai
Ito, Yuko
Naoe, Satoko
Kojima, Kotoe
Ikeguchi, Mitsunori
Arita, Makoto
author_sort Isobe, Yosuke
collection PubMed
description Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selected and identified to confer omega-3 epoxidation of EPA to yield 17,18-epoxyeicosatetraenoic acid (17,18-EpETE). Stereoselective production of 17,18-EpETE by each CYP isoform was confirmed, and molecular modeling indicated that chiral differences stem from different EPA binding conformations in the catalytic domains of respective CYP enzymes.
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spelling pubmed-59626382018-05-24 Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid Isobe, Yosuke Itagaki, Mai Ito, Yuko Naoe, Satoko Kojima, Kotoe Ikeguchi, Mitsunori Arita, Makoto Sci Rep Article Metabolites generated via oxygenation of the omega-3 double bond (omega-3 oxygenation) in eicosapentaenoic acid (EPA) have recently been identified as novel anti-inflammatory lipid mediators. Therefore, oxygenase(s) responsible for this metabolic pathway are of particular interest. We performed genome-wide screening of mouse cytochrome P450 (CYP) isoforms to explore enzymes involved in omega-3 oxygenation of EPA. As a result, 5 CYP isoforms (mouse Cyp1a2, 2c50, 4a12a, 4a12b, and 4f18) were selected and identified to confer omega-3 epoxidation of EPA to yield 17,18-epoxyeicosatetraenoic acid (17,18-EpETE). Stereoselective production of 17,18-EpETE by each CYP isoform was confirmed, and molecular modeling indicated that chiral differences stem from different EPA binding conformations in the catalytic domains of respective CYP enzymes. Nature Publishing Group UK 2018-05-21 /pmc/articles/PMC5962638/ /pubmed/29784972 http://dx.doi.org/10.1038/s41598-018-26325-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Isobe, Yosuke
Itagaki, Mai
Ito, Yuko
Naoe, Satoko
Kojima, Kotoe
Ikeguchi, Mitsunori
Arita, Makoto
Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title_full Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title_fullStr Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title_full_unstemmed Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title_short Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
title_sort comprehensive analysis of the mouse cytochrome p450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962638/
https://www.ncbi.nlm.nih.gov/pubmed/29784972
http://dx.doi.org/10.1038/s41598-018-26325-4
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