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Elucidation of novel archaeal mevalonate pathways oriented to metabolic engineering application

Research Project

Project/Area Number 23580111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied microbiology
Research InstitutionNagoya University

Principal Investigator

HEMMI Hisashi  名古屋大学, 生命農学研究科, 准教授 (60302189)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords酵素 / 微生物 / 生体分子 / イソプレノイド / メバロン酸経路 / アーキア / 代謝 / フラビン酵素
Research Abstract

A part of reactions in the archaeal mevalonate pathways were unidentified. Thus we performed the conversion assay of radio-labeled substrates by cell-free extract from archaea and functional characterization of archaeal homologs of known mevalonate pathway-related enzymes. As the result, we discovered the classical mevalonate pathway, which is rare in archaea, from an archaeon of genus Sulfolobus, and a novel modified pathway, which passes through 3-phosphomevalonate, from an archaeon of genus Thermoplasma.
We also performed X-ray crystal structural studies on type 2 isopentenyl diphosphate isomerase and diphosphomevalonate decarboxylase from archaea of genus Sulfolobus. The obtained structures and the results of various analyses showed novel mechanisms of catalysis, regulation of activity, and thermostabilization.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (47 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (33 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] (R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum2014

    • Author(s)
      Azami, Y., Hattori, A., Nishimura, H., Kawaide, H., Yoshimura, T. & Hemmi, H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Geranylgeranyl reductase and ferredoxin from Methanosarcina acetivorans are required for the synthesis of fully reduced archaeal membrane lipid in Escherichia coli cells.2014

    • Author(s)
      Isobe, K. et al.
    • Journal Title

      Journal of Bacteriology

      Volume: 196 Issue: 2 Pages: 417-423

    • DOI

      10.1128/jb.00927-13

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] (R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum2014

    • Author(s)
      Azami, Y. et al.
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Issue: 23 Pages: 15957-15967

    • DOI

      10.1074/jbc.m114.562686

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical evidence supporting the presence of the classical mevalonate pathway in the thermoacidophilic archaeon Sulfolobus solfataricus2013

    • Author(s)
      Nishimura, H., Azami, Y., Miyagawa, M., Hashimoto, C., Yoshimura, T. & Hemmi, H.
    • Journal Title

      Journal of Biochemistry

      Volume: vol. 153 Pages: 415-420

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Substrate specificity of undecaprenyl diphosphate synthase from the hyperthermophilic archaeon Aeropyrum pernix.2013

    • Author(s)
      Mori, T. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 436 Issue: 2 Pages: 230-234

    • DOI

      10.1016/j.bbrc.2013.05.081

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical evidence supporting the presence of the classical mevalonate pathway in the thermoacidophilic archaeon Sulfolobus solfataricus.2013

    • Author(s)
      Nishimura, H. et al.
    • Journal Title

      Journal of Biochemistry

      Volume: in press Issue: 5 Pages: 415-420

    • DOI

      10.1093/jb/mvt006

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Substrate-induced change in the quaternary structure of type 2 isopentenyl diphosphate isomerase from Sulfolobus shibatae2012

    • Author(s)
      Nakatani, H., Goda, S., Unno, H., Nagai, T., Yoshimura, T. & Hemmi, H.
    • Journal Title

      Journal of Bacteriology

      Volume: vol. 194 Pages: 3216-3224

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Substrate-induced change in the quaternary structure of type 2 isopentenyl diphosphate isomerase from Sulfolobus shibatae2012

    • Author(s)
      Nakatani, H.
    • Journal Title

      J.Bacteriol.

      Volume: 194(in press) Issue: 12 Pages: 3216-3224

    • DOI

      10.1128/jb.00068-12

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Archaeal phospholipid biosynthetic pathway reconstructed in Escherichia coli.2012

    • Author(s)
      Yokoi, T. et al.
    • Journal Title

      Archaea

      Volume: 2012 Pages: 1-9

    • DOI

      10.1155/2012/438931

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors2011

    • Author(s)
      Nagai, T., Unno, H., Janczak, M.W., Yoshimura, T., Poulter, C.D. & Hemmi, H.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: vol. 108 Pages: 20461-20466

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structure and mutation analysis of archaeal geranylgeranyl reductase2011

    • Author(s)
      Sasaki, D., Fujihashi, M., Iwata, Y., Murakami, M., Yoshimura, T., Hemmi, H. & Miki, K.
    • Journal Title

      Journal of Molecular Biology

      Volume: 409 Pages: 543-557

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Connected cavity structure enables prenyl elongation across the dimer interface in mutated geranylfarnesyl diphosphate synthase from Methanosarcina mazei2011

    • Author(s)
      Ogawa, T., Yoshimura, T. & Hemmi, H.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 409 Pages: 333-337

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] A third alternative mevalonate pathway from Thermoplasma acidophilum2014

    • Author(s)
      Hisashi Hemmi, Yasuhiro Azami, Ai Hattori, Hiroshi Kawaide and Tohru Yoshimura
    • Organizer
      1^<st> US-Japan Seminar on the Biosynthesis of Natural Products for Young Researchers
    • Place of Presentation
      Tokyo Institute of Technology
    • Related Report
      2013 Final Research Report
  • [Presentation] A third alternative mevalonate pathway from Thermoplasma acidophilum2014

    • Author(s)
      Hisashi Hemmi et al.
    • Organizer
      US-Japan Seminar on the Biosynthesis of Natural Products For Young Researcher
    • Place of Presentation
      Tokyo Technology Institute
    • Related Report
      2013 Annual Research Report
  • [Presentation] 好熱好酸性アーキアSulfolobus solfataricus由来ジホスホメバロン酸デカルボキシラーゼの立体構造2013

    • Author(s)
      服部愛、海野英昭、吉村徹、邊見久
    • Organizer
      第23回イソプレノイド研究会例会
    • Place of Presentation
      東京大学農学部中島董一郎ホール
    • Year and Date
      2013-09-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 好熱性アーキア由来ジホスホメバロン酸デカルボキシラーゼの結晶構造解析2013

    • Author(s)
      服部愛、海野英昭、吉村徹、邊見久
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] タイプ2イソペンテニル二リン酸イソメラーゼにおけるフラビン補酵素の触媒機能2013

    • Author(s)
      邊見久
    • Organizer
      2013年度日本農芸化学会大会
    • Place of Presentation
      東北大学
    • Related Report
      2013 Final Research Report
  • [Presentation] 好熱性アーキア由来ジホスホメバロン酸デカルボキシラーゼの結晶構造解析2013

    • Author(s)
      服部 愛ら
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 好熱好酸性アーキアSulfolobus solfataricus由来ジホスホメバロン酸デカルボキシラーゼの立体構造2013

    • Author(s)
      服部 愛ら
    • Organizer
      第23回イソプレノイド研究会例会
    • Place of Presentation
      東京大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] タイプ2イソペンテニル二リン酸イソメラーゼにおけるフラビン補酵素の触媒機能2013

    • Author(s)
      邊見 久
    • Organizer
      2013年度日本農芸化学会大会
    • Place of Presentation
      東北大学(仙台市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 基質により誘導される好熱性アーキア由来タイプ2イソペンテニル二リン酸イソメラーゼの四次構造変化2012

    • Author(s)
      中谷仁美、郷田秀一郎、海野英昭、長井拓也、吉村徹、邊見久
    • Organizer
      第22回ドリコールおよびイソプレノイド研究会例会
    • Place of Presentation
      新潟大学駅南キャンパス「ときめいと」
    • Year and Date
      2012-09-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Substrate-induced change in the quaternary structure of type 2 isopentenyl diphosphate isomerase from Sulfolobus shibatae2012

    • Author(s)
      Hisashi Hemmi
    • Organizer
      新学術領域「生合成マシナリー」第4回若手シンポジウム(第8回生合成勉強会)
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2012-08-25
    • Related Report
      2013 Final Research Report
  • [Presentation] mechanism-based inhibitorを用いたタイプ2イソペンテニル二リン酸イソメラーゼの反応機構解析2012

    • Author(s)
      邊見久
    • Organizer
      2012年度酵素・補酵素研究会
    • Place of Presentation
      名古屋大学野依記念学術交流館
    • Related Report
      2013 Final Research Report
  • [Presentation] Sulfolobus solfataricusにおけるメバロン酸経路の酵素学的研究2012

    • Author(s)
      生明靖裕、西村泰斗、吉村徹、邊見久
    • Organizer
      日本Archaea研究会第25回講演会
    • Place of Presentation
      関西学院大学西宮上ヶ原キャンパス
    • Related Report
      2013 Final Research Report
  • [Presentation] 好熱性アーキア由来タイプ2イソペンテニル二リン酸イソメラーゼの四次構造に対する基質結合の影響2012

    • Author(s)
      中谷仁美、郷田秀一郎、海野英昭、長井拓也、吉村徹、邊見久
    • Organizer
      2012年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Archaeal phospholipid biosynthesis pathway reconstructed in E. coli2012

    • Author(s)
      Hisashi Hemmi
    • Organizer
      The International Conference of Natural Product Biosynthesis
    • Place of Presentation
      Awaji, Hyogo, Japan
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Chain length determination mechanism of geranylfarnesyl diphosphate synthase from methanogenic archaeon Methanosarcina mazei2012

    • Author(s)
      Takuya Ogawa
    • Organizer
      The International Conference of Natural Product Biosynthesis
    • Place of Presentation
      Awaji, Hyogo, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Sulfolobus solfataricusにおけるメバロン酸経路の酵素学的研究2012

    • Author(s)
      生明靖裕
    • Organizer
      日本Archaea研究会第25回講演会
    • Place of Presentation
      関西学院大学(西宮市)
    • Related Report
      2012 Research-status Report
  • [Presentation] mechanism-based inhibitorを用いたタイプ2イソペンテニル二リン酸イソメラーゼの反応機構解析2012

    • Author(s)
      邊見 久
    • Organizer
      2012年度酵素・補酵素研究会
    • Place of Presentation
      名古屋大学(名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 生合成マシナリーへのアーキア酵素組み込みによる非天然イソプレノイド化合物の創出2012

    • Author(s)
      邊見 久
    • Organizer
      新学術領域「生合成マシナリー」第4回公開シンポジウム
    • Place of Presentation
      東京大学(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 代謝経路再構築によるアーキア膜脂質の大腸菌細胞における生産2012

    • Author(s)
      磯部圭祐
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場(博多市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 大腸菌での代謝経路再構築によるアーキア型膜脂質の生産2012

    • Author(s)
      磯部圭祐、横井 宇、吉村 徹、邊見 久
    • Organizer
      2012年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 好熱性アーキア由来タイプ2イソペンテニル二リン酸イソメラーゼの四次構造に対する基質結合の影響2012

    • Author(s)
      中谷仁美、郷田秀一郎、海野英昭、長井拓也、吉村 徹、邊見 久
    • Organizer
      2012年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Sulfolobus属アーキアにおける古典的メバロン酸経路の酵素学的研究2011

    • Author(s)
      西村泰斗、橋本知佳、吉村徹、邊見久
    • Organizer
      第21回ドリコールおよびイソプレノイド研究会例会
    • Place of Presentation
      島根大学大学会館
    • Year and Date
      2011-11-04
    • Related Report
      2013 Final Research Report
  • [Presentation] タイプ2イソペンテニル二リン酸イソメラーゼにおけるフラビン補酵素の機能2011

    • Author(s)
      邊見久
    • Organizer
      新学術領域「生合成マシナリー」第2回若手シンポジウム(第6回生合成勉強会)
    • Place of Presentation
      理研鈴木梅太郎ホール(和光市)
    • Year and Date
      2011-07-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Non-redox catalysis by reduced flavin mononucleotide in type 2 isopentenyl diphosphate isomerase2011

    • Author(s)
      Hisashi Hemmi
    • Organizer
      17^<th> International Symposium on Flavins and Flavoprotein
    • Place of Presentation
      University of California, Berkeley
    • Related Report
      2013 Final Research Report
  • [Presentation] 不可逆阻害剤となる基質アナログを用いたタイプ2イソペンテニル二リン酸イソメラーゼの反応機構解析2011

    • Author(s)
      邊見久、長井拓也、海野英昭、吉村徹
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      安田女子大学(広島市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 不可逆阻害剤となる基質アナログを用いたタイプ2イソペンテニル二リン酸イソメラーゼの反応機構解析2011

    • Author(s)
      邊見 久、長井拓也、海野英昭、吉村 徹
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      安田女子大学(広島市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Non-redox catalysis by reduced flavin mononucleotide in type 2 isopentenyl diphosphate isomerase2011

    • Author(s)
      Hisashi Hemmi
    • Organizer
      17th International Symposium on Flavins and Flavoproteins(招待講演)
    • Place of Presentation
      University of California, Berkeley (USA)
    • Related Report
      2011 Research-status Report
  • [Presentation] Structure-function relationship in archaeal geranylgeranyl reductase2011

    • Author(s)
      Hisashi Hemmi, Yuki Iwata, Daisuke Sasaki, Masahiro Fujihashi, Motomichi Murakami, Tohru Yoshimura, and Kunio Miki
    • Organizer
      Gordon Research Conference on Archaea: Ecology, Metabolism & Molecular Biology
    • Place of Presentation
      Waterville Valley Resort, New Hampshire (USA)
    • Related Report
      2011 Research-status Report
  • [Presentation] アーキア膜脂質の大腸菌における生産2011

    • Author(s)
      磯部圭祐、横井 宇、吉村 徹、邊見 久
    • Organizer
      日本Archaea研究会第24回講演会
    • Place of Presentation
      慶応義塾大学先端生命科学研究所(鶴岡市)
    • Related Report
      2011 Research-status Report
  • [Presentation] アーキア膜脂質生合成に関わるゲラニルゲラニルレダクターゼの構造機能相関2011

    • Author(s)
      邊見 久
    • Organizer
      第84回日本生化学会大会(招待講演)
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Sulfolobus属アーキアにおける古典的メバロン酸経路の酵素学的研究2011

    • Author(s)
      西村泰斗、橋本知佳、吉村 徹、邊見 久
    • Organizer
      第21回ドリコールおよびイソプレノイド研究会例会
    • Place of Presentation
      島根大学大学会館(松江市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Substrate-induced change in the quaternary structure of type 2 isopentenyl diphosphate isomerase from Sulfolobus shibatae

    • Author(s)
      邊見 久
    • Organizer
      新学術領域「生合成マシナリー」第4回若手シンポジウム
    • Place of Presentation
      静岡県立大学(静岡市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 基質により誘導される好熱性アーキア由来タイプ2イソペンテニル二リン酸イソメラーゼの四次構造変化

    • Author(s)
      中谷仁美
    • Organizer
      第22回ドリコールおよびイソプレノイド研究会例会
    • Place of Presentation
      新潟大学(新潟市)
    • Related Report
      2012 Research-status Report
  • [Book] Handbook of Flavoproteins : Volume 1–Oxidases, Dehydrogenases and Related Systems2012

    • Author(s)
      Hemmi, H. et al.
    • Publisher
      Walter de Gruyter
    • Related Report
      2013 Final Research Report
  • [Book] Handbook of Flavoproteins: Volume 1ーOxidases, Dehydrogenases and Related Systems2012

    • Author(s)
      Hisashi Hemmi et al.
    • Total Pages
      358
    • Publisher
      de Gruyter
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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