TY - JOUR
T1 - Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid
AU - Isobe, Yosuke
AU - Itagaki, Mai
AU - Ito, Yuko
AU - Naoe, Satoko
AU - Kojima, Kotoe
AU - Ikeguchi, Mitsunori
AU - Arita, Makoto
N1 - Funding Information:
This work was funded in part by the Japan Society for the Promotion of Science KAKENHI JP15H05897, 15H05898, 15H04648 (M.A.), Grants-in-Aid for Young Scientists (B) JP26860034 (Y.I.), RIKEN Special Postdoctoral Researcher Program (Y.I.), and the Program for Promotion of Basic and Applied Research for Innovations in Bio-Oriented Industry (M.A.). We thank the FANTOM consortium for providing clones for the mouse CYP family.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-018-26325-4
DO - 10.1038/s41598-018-26325-4
M3 - Article
C2 - 29784972
AN - SCOPUS:85047299452
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 7954
ER -