Creation of novel P450 enzymes with high metabolizing activities toward polychlorinated biphenyls and modification of its intracellular localization
Project/Area Number |
25550064
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Modeling and technologies for environmental conservation and remediation
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Research Institution | Kobe University |
Principal Investigator |
INUI Hideyuki 神戸大学, 遺伝子実験センター, 准教授 (90314509)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | ポリ塩化ビフェニル / P450 / 代謝 / 水質汚濁・土壌汚染防止・ 浄化 |
Outline of Final Research Achievements |
Polychlorinated biphenyls (PCBs) show toxicity such as carcinogenicity through bioaccumulation because of its high lipophilicity and persistency. Identification of P450 monooxygenases metabolizing PCBs, creation of novel P450s with high metabolizing activities, and modification of intracellular localization of P450s were attempted to achieve remediation of PCBs in the environment. One of PCB congeners, CB118 was metabolized by human CYP2B6 to hydroxylated metabolites due to proximity of the active center of P450s and CB118. Furthermore, P450 mutants contributed decrease of PCB toxicity, and P450s were localized in a plasma membrane. These results showed that we established basic technologies on high metabolism of PCBs by creation of P450s with high metabolizing activities and localization of P450s.
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Report
(3 results)
Research Products
(12 results)
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[Presentation] Structural basis of metabolism of 2,3',4,4',5-pentachlorobiphenyl (CB118) by mammalian cytochrome P450 monooxygenases2014
Author(s)
Shintarou Mise, Yuuki Haga, Miku Yabu, Toshimasa Itoh, Keiko Yamamoto, Chisato Matsumura, Takeshi Nakano, Toshiyuki Sakaki, Hideyuki Inui
Organizer
International Conference of Asian Environmental Chemistry 2014
Place of Presentation
Bangkok (Thailand)
Year and Date
2014-11-24
Related Report
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[Presentation] Amino acid variations in mammalian cytochrome P450 monooxygenases responsible for decrease of dioxin-like toxicity of polychlorinated biphenyls2013
Author(s)
Hideyuki Inui, Kiyoshi Yamazaki, Miku Yabu, Toshimasa Itoh, Keiko Yamamoto, Motoharu Suzuki, Yuuki Haga, Shintarou Mise, Masahiro Tsurukawa, Chisato Matsumura, Takeshi Nakano, Toshiyuki Sakaki
Organizer
33nd International Symposium on Halogenated Persistent Organic Pollutants
Place of Presentation
Daegu, Korea
Related Report
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