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Creation of novel P450 enzymes with high metabolizing activities toward polychlorinated biphenyls and modification of its intracellular localization

Research Project

Project/Area Number 25550064
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Modeling and technologies for environmental conservation and remediation
Research InstitutionKobe University

Principal Investigator

INUI Hideyuki  神戸大学, 遺伝子実験センター, 准教授 (90314509)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
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)
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.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Invited: 4 results) Remarks (2 results)

  • [Journal Article] Mammalian cytochrome P450-dependent metabolism of polychlorinated dibenzo-p-dioxins and coplanar polychlorinated biphenyls2014

    • Author(s)
      Inui, H., Itoh, T., Yamamoto, K., Ikushiro, S.-I., Sakaki, T.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 15(8) Issue: 8 Pages: 14044-14057

    • DOI

      10.3390/ijms150814044

    • NAID

      120005647292

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Structural basis of species differences on metabolism and toxicity of polychlorinated biphenyls among mammals2015

    • Author(s)
      Hideyuki Inui
    • Organizer
      The Serbian Biochemical Society
    • Place of Presentation
      Belgrade (Serbia)
    • Year and Date
      2015-06-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 哺乳類シトクロムP450モノオキシゲナーゼによるポリ塩化ビフェニルの毒性低下メカニズム2015

    • Author(s)
      見世慎太朗、加藤晃、伊藤俊将、山本恵子、乾秀之
    • Organizer
      2015年度日本農芸化学会
    • Place of Presentation
      岡山大学(岡山)
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [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
      2014 Annual Research Report
  • [Presentation] Mammalian cytochrome P450-dependent metabolism of polychlorinated dibenzo-p-dioxins and coplanar polychlorinated biphenyls, and application to bioremediation2014

    • Author(s)
      Hideyuki Inui, Shintarou Mise, Toshimasa Itoh, Keiko Yamamoto, Shin-Ichi Ikushiro, and Toshiyuki Sakaki
    • Organizer
      The 12th International Symposium on Cytochrome P450 Biodiversity & Biotechnology
    • Place of Presentation
      京都市国際交流会館(京都)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structural Basis of Species Differences in Metabolism of Polychlorinated Biphenyls2014

    • Author(s)
      Hideyuki Inui
    • Organizer
      23nd Symposium on Environmental Chemistry
    • Place of Presentation
      京都大学(京都)
    • Year and Date
      2014-05-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Structural Basis of Species Differences between Rat and Human CYP1A1s in Metabolism of Polychlorinated Biphenyls2014

    • Author(s)
      Hideyuki Inui
    • Organizer
      e-symposium
    • Place of Presentation
      Osaka
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ラットおよびヒト由来シトクロムP450モノオキシゲナーゼによるCB118の代謝と3次元構造の比較2013

    • Author(s)
      見世慎太朗、羽賀雄紀、薮未来、伊藤俊将、山本恵子、鶴川正寛、松村千里、中野武、榊利之、乾秀之
    • Organizer
      第22回環境化学討論会
    • Place of Presentation
      東京農工大学
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural Basis of Species Differences between Rat and Human CYP1A1s in Metabolism of Polychlorinated Biphenyls2013

    • Author(s)
      Hideyuki Inui
    • Organizer
      22nd Symposium on Environmental Chemistry
    • Place of Presentation
      東京農工大学
    • Related Report
      2013 Research-status Report
    • Invited
  • [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
      2013 Research-status Report
  • [Remarks] 神戸大学 遺伝子実験センター 環境遺伝子機能解析研究分野 乾グループ

    • URL

      http://www.research.kobe-u.ac.jp/rceg/doc./inui/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 神戸大学 遺伝子実験センター 環境遺伝子機能解析研究分野 乾グループ

    • URL

      http://www.research.kobe-u.ac.jp/rceg/doc./inui/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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