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Screening of natural products which inhibits a new menaquinone biosynthetic pathway

Research Project

Project/Area Number 22310139
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionHokkaido University

Principal Investigator

DAIRI Tohru  北海道大学, 大学院・工学研究院, 教授 (70264679)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Keywords微生物 / メナキノン / 生合成 / フタロシン経路 / 阻害剤 / フタロシン / ピロリ菌 / Radical SAM / futalosine hydrolase / futalosine / aminodeoxy futalosine / inhibitor
Research Abstract

The futalosine pathway is operating in some bacteria for the biosynthesis of menaquinone. Futalosine is converted into dehypoxanthinyl futalosine (DHFL) by MqnB.In this study, three routes to the formation of DHFL were suggested. DHFL may have been directly formed by MqnB in Thermus thermophilus. In Streptomyces coelicolor, aminodeoxy FL (AFL) was converted to FL by deaminases, then to DHFL. In contrast, MqnB of Helicobacter pylori directly converted AFL into DHFL.
To identify compounds that specifically inhibit the futalosin pathway, we used B. halodurans that has FL pathway as a test strain. Finally, two candidate fungal culture broths were obtained.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (48 results)

All 2013 2012 2011 2010 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (25 results) (of which Invited: 1 results) Book (2 results) Remarks (4 results)

  • [Journal Article] CcpAx is a new member of the cellulose synthase complex (terminal complex) in Acetobacter xylinum2013

    • Author(s)
      N. Sunagawa, T. Fujiwara, T. Yoda, D.Shimura, M. Sakai, S. Kawano, Y. Satoh, M. Yao, K. Tajima, and T. Dairi
    • Journal Title

      J. Biosci. Bioeng

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CcpAx is a new member of the cellulose synthase complex (terminal complex) in Acetobacter xylinum2013

    • Author(s)
      N. Sunagawa, T. Fujiwara, T. Yoda, D. Shimura, M. Sakai, S. Kawano, Y. Satoh, M. Yao, K. Tajima, and T. Dairi
    • Journal Title

      J. Biosci. Bioeng

      Volume: in press Issue: 6 Pages: 607-612

    • DOI

      10.1016/j.jbiosc.2012.12.021

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellulose production by Enterobacter sp. CJF-002 and identification of genes for cellulose biosynthesis2012

    • Author(s)
      N. Sunagawa, K. Tajima, M. Hosoda, S. Kawano, Y. Satoh, M. Yao, T. Dairi
    • Journal Title

      Cellulose

      Volume: 19 Issue: 6 Pages: 1989-2001

    • DOI

      10.1007/s10570-012-9777-2

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Menaquinone biosyntheses in microorganisms.2012

    • Author(s)
      Dairi T.
    • Journal Title

      Methods Enzymol

      Volume: 515 Pages: 107-122

    • DOI

      10.1016/b978-0-12-394290-6.00006-9

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of (±)-cyclic de-hypoxanthine futalosine, the biosynthetic intermediate in an alternative biosynthetic pathway for menaquinones.2011

    • Author(s)
      A. Yajima, S. Kouno, M. Mogi, R. Katsuta, T. Dairi, H. Seto, and T. Nukada
    • Journal Title

      Tetrahedron Lett.

      Volume: 52 Pages: 4934-4937

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of a Thermotolerant Bacterium Producing Medium-chain-length Polyhydroxyalkanoate2011

    • Author(s)
      Y. Satoh, K. Tajima, S. Nakamoto, H.Xuerong, T. Matsushima, T. Ohshima, S. Kawano, T. Erata, T. Dairi, and M. Munekata
    • Journal Title

      J. Appl. Microbiol.

      Volume: 111 Pages: 811-817

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enzymatic polymerization of 2-hydroxyalkanoates: copolymerization of 2-hydroxybutyrate by wild-type class I PHA synthase.2011

    • Author(s)
      X. Han, Y. Satoh, T. Satoh, T. Kakuchi, K.Matsumoto, S. Taguchi, T. Dairi, M. Munekata, and K. Tajima
    • Journal Title

      Appl. Microbiol. Biotech.

      Volume: 92 Pages: 509-517

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation2011

    • Author(s)
      S. Takahashi, A. Toyoda, Y. Sekiyama, H.Takagi, T. Nogawa, M. Uramoto, R. Suzuki, H. Koshino, T. Kumano, S. Panthee, T. Dairi, J. Ishikawa, H. Ikeda, Y. Sakaki, and H. Osada
    • Journal Title

      Nat. Chem. Biol.

      Volume: 7 Pages: 461-468

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Convergent strategies in biosynthesis.2011

    • Author(s)
      T. Dairi, T. Kuzuyama, M. Nishiyama, and Fujii I.
    • Journal Title

      Nat. Prod. Rep.

      Volume: 28 (6) Pages: 1054-1086

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diversity of the early step of the futalosine pathway.2011

    • Author(s)
      C. Arakawa, K. Furihata, T. Hiratsuka, N.Itoh, H. Seto, and T. Dairi
    • Journal Title

      Antimicrob Agents Chemother.

      Volume: 55 Pages: 913-916

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dairi, Branched fatty acids inhibit the biosynthesis of menaquinone in Helicobacter pylori.2011

    • Author(s)
      R. Tanaka, T. Kunisada, N. Kushida, K.Yamada, S. Ikeda, M. Noike, Y. Ono, N. Itoh, H. Takami, H. Seto, and T.
    • Journal Title

      J. Antibiot.

      Volume: 64 Pages: 151-153

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 微生物におけるビタミンK生合成の分子機構と生物学的意義2011

    • Author(s)
      大利徹
    • Journal Title

      腎と代謝

      Volume: 24巻 Pages: 179-186

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Journal Article] Convergent strategies in biosynthesis2011

    • Author(s)
      T.Dairi, T.Kuzuyama, M.Nishiyama, Fujii I
    • Journal Title

      Nat.Prod.Rep.

      Volume: 28 Issue: 6 Pages: 1054-1086

    • DOI

      10.1039/c0np00047g

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of (±)-cyclic de-hypoxanthine futalosine, the biosynthetic intermediate in an alternative biosynthetic pathway for menaquinones2011

    • Author(s)
      A.Yajima, S.Kouno, M.Mogi, R.Katsuta, T.Dairi, H.Seto, T.Nukada
    • Journal Title

      Tetrahedron Lett.

      Volume: 52 Issue: 38 Pages: 4934-4937

    • DOI

      10.1016/j.tetlet.2011.07.061

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Branched fatty acids inhibit the biosynthesis of menaquinone in Helicobacter pylori.2011

    • Author(s)
      R.Tanaka, T.Kunisada, N.Kushida, K.Yamada, S.Ikeda, M.Noike, Y.Ono, N.Itoh, H.Takami, H.Seto, T.Dairi
    • Journal Title

      J.Antibiot.

      Volume: 64 Pages: 151-153

    • NAID

      10030637951

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diversity of the early step of the futalosine pathway.2011

    • Author(s)
      C.Arakawa, K.Furihata, T.Hiratsuka, N.Itoh, H.Seto, T.Dairi
    • Journal Title

      Antimicrob. Agents Chemother.

      Volume: 55 Pages: 913-916

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the Lactobacillus metabolic pathway.2010

    • Author(s)
      M.Kuratsu, Y.Hamano, T.Dairi
    • Journal Title

      Appl.Environ.Microbiol.

      Volume: 76 Pages: 7299-7301

    • NAID

      120002973851

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規メナキノン生合成経路酵素MqnDの生成物・類似体複合体のX線結晶構造解析2013

    • Author(s)
      松尾京子、石北央、大利徹、瀬戸治男、新井亮一
    • Organizer
      平成25年度日本農芸化学会大会
    • Place of Presentation
      東北大学
    • Related Report
      2012 Final Research Report
  • [Presentation] 放線菌が持つメナキノン新規生合成経路の解明と特異的阻害剤の探索2012

    • Author(s)
      池田駿介、池田安由美、佐藤康治、野池基義、瀬戸治男、大利徹
    • Organizer
      2012年度(第27回)日本放線菌学会大会
    • Place of Presentation
      府中の森芸術劇場
    • Year and Date
      2012-09-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 補酵素類の生合成に関与する新規酵素の解析と応用2012

    • Author(s)
      大利徹
    • Organizer
      第13回酵素応用シンポジウム
    • Place of Presentation
      名古屋メルパルク
    • Year and Date
      2012-06-08
    • Related Report
      2012 Final Research Report
  • [Presentation] 微生物に見出されたメナキノ ン新規生合成経路の全容解明と抗ピロ リ菌薬開発への応用2012

    • Author(s)
      大利徹
    • Organizer
      公益財団法人発酵研究所第6回研究報告会
    • Place of Presentation
      千里ライフ サイエンスセンター 大阪
    • Year and Date
      2012-06-07
    • Related Report
      2012 Final Research Report
  • [Presentation] 微生物に見出されたメナキノン新規生合成経路の全容解明と抗ピロ リ菌剤の開発2012

    • Author(s)
      大利徹
    • Organizer
      公益財団法人野田産業科学研究所、平成24年度研究成果発表会
    • Place of Presentation
      東京会館
    • Year and Date
      2012-06-01
    • Related Report
      2012 Final Research Report
  • [Presentation] フタロシン(FL)経路の解析2012

    • Author(s)
      池田駿介、柏崎恭平、小野裕介、池田安由美、佐藤康治、矢島新、瀬戸治男、大利徹
    • Organizer
      平成24年度 日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都市)
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] バクテリアにおける新規葉酸生合成経路の解明2012

    • Author(s)
      佐藤康治、大利徹
    • Organizer
      平成24年度 日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都市)
    • Year and Date
      2012-03-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to Helicobacter pylori2012

    • Author(s)
      Tohru Dairi
    • Organizer
      17th Malaysian Chemical Congress (17MCC)
    • Place of Presentation
      Putra World Trade Centre, Kuala Lumpur, Malaysia.
    • Related Report
      2012 Final Research Report
  • [Presentation] 放線菌が持つメナキノン新規生合成経路の解明と特異的阻害剤の探索2012

    • Author(s)
      池田駿介、池田安由美、佐藤康治、野池基義、瀬戸治男、大利 徹
    • Organizer
      2012年度(第27回)日本放線菌学会大会
    • Place of Presentation
      府中の森芸術劇場(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to Helicobacter pylori2012

    • Author(s)
      Tohru Dairi
    • Organizer
      17th Malaysian Chemical Congress
    • Place of Presentation
      Putra World Trade Centre, Kuala Lumpur, Malaysia
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Microorganisms evolved vitamin biosynthetic enzymes in response to various environments, an example in menaquinone biosynthesis2011

    • Author(s)
      Tohru Dairi
    • Organizer
      IUMS 2011
    • Place of Presentation
      札幌国際会議場(札幌市)(招待講演)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Search for a new metabolic pathway by genome mining in Streptomyces coelicolor2011

    • Author(s)
      Kentaro Yanashima, Tomomi Matsui, Shunsuke Ikeda, Tohru Dairi
    • Organizer
      日本放線菌学会2011年度大会
    • Place of Presentation
      札幌国際会議場(札幌市)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] An alternative menaquinone biosynthetic pathway : an attractive target for drug discovery to Helicobacter pylori2011

    • Author(s)
      Tohru Dairi
    • Organizer
      The Third International Conference on Cofactors 03 (ICC-03)
    • Place of Presentation
      The University of Turku, (Finland)(招待講演)
    • Year and Date
      2011-07-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 微生物におけるビタミン生合成経路の多様性2011

    • Author(s)
      大利徹
    • Organizer
      生物資源学特別セミナー
    • Place of Presentation
      福井県立大学
    • Year and Date
      2011-05-23
    • Related Report
      2012 Final Research Report
  • [Presentation] Microorganisms evolved vitamin biosynthetic enzymes in response to various environments, an example in menaquinone biosynthesis2011

    • Author(s)
      Tohru Dairi
    • Organizer
      The IUMS2011, Sapporo
    • Place of Presentation
      札幌国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to Helicobacter pylori2011

    • Author(s)
      Tohru Dairi
    • Organizer
      The Third International Conference on Cofactors 03 (ICC-03)
    • Place of Presentation
      The University of Turku, Finland
    • Related Report
      2012 Final Research Report
  • [Presentation] メナキノン(MK)新規生合成経路阻害剤の探索2011

    • Author(s)
      田中友理、國定孝夫、櫛田伸明、山田恵子、池田駿介、伊藤伸哉、瀬戸治男、大利徹
    • Organizer
      平成23年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Related Report
      2012 Final Research Report
  • [Presentation] フタロシン(FL)経路の初発反応の多様性2011

    • Author(s)
      荒川知里、倉都将宏、伊藤伸哉、瀬戸治男、大利徹
    • Organizer
      平成23年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学
    • Related Report
      2012 Final Research Report
  • [Presentation] Studies on the early biosynthetic step of the futalosine (menaquinone) pathway2010

    • Author(s)
      Tohru Dairi
    • Organizer
      Pacifichem 2010,Honolulu
    • Place of Presentation
      シェラトンワイキキ
    • Year and Date
      2010-12-16
    • Related Report
      2012 Final Research Report
  • [Presentation] ピロリ菌が持つ特異的ビタミン生合成経路の解明と抗ピロリ菌薬開発への挑戦2010

    • Author(s)
      大利徹
    • Organizer
      第3回北大工学系-道総研連携フォーラム
    • Place of Presentation
      北大創成科学研究棟
    • Year and Date
      2010-10-26
    • Related Report
      2012 Final Research Report
  • [Presentation] An alternative menaquinone biosynthetic pathway: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains.2010

    • Author(s)
      Tohru Dairi
    • Organizer
      12th Japanese-Swiss Meeting on Biotechnology and BioprocessDevelopment, Toyama
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2010-10-11
    • Related Report
      2012 Final Research Report
  • [Presentation] 放線菌におけるフタロシン経路の初発反応の多様性2010

    • Author(s)
      荒川知里、倉都将宏、瀬戸治男、大利徹
    • Organizer
      平成22年度日本放線菌学会大会
    • Place of Presentation
      東京、タワーホール船堀
    • Year and Date
      2010-09-03
    • Related Report
      2012 Final Research Report
  • [Presentation] 放線菌が持つメナキノン新規 生合成経路の解明2010

    • Author(s)
      大利徹
    • Organizer
      平成22年度日本放線菌学会大会
    • Place of Presentation
      東京、タワーホール船堀
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] 微生物に見出されたメナキノン新規生合成の解明にいたるストーリ ィー2010

    • Author(s)
      大利徹
    • Organizer
      第45回天然物化学談話会
    • Place of Presentation
      愛知県蒲郡市、ホテル明山荘
    • Year and Date
      2010-07-07
    • Related Report
      2012 Final Research Report
  • [Presentation] 微生物に見出されたメナキノン新規生合成の解明にいたるストーリィー2010

    • Author(s)
      大利徹
    • Organizer
      第45回天然物化学談話会
    • Place of Presentation
      三谷温泉ホテル明山荘愛知県蒲郡市 招待講演
    • Year and Date
      2010-07-07
    • Related Report
      2010 Annual Research Report
  • [Book] Isoprenoid Synthesis in Plants and Microorganisms2013

    • Author(s)
      Tohru Dairi(分担執筆)
    • Total Pages
      493
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Book] Methods in Enzymol2012

    • Author(s)
      T. Dairi
    • Publisher
      Menaquinone biosyntheses in microorganisms
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.eng.hokudai.ac.jp/labo/tre/

    • Related Report
      2012 Final Research Report
  • [Remarks] 研究成果

    • URL

      http://www.eng.hokudai.ac.jp/labo/tre/ABCLab_jp/index.php?ARTICLE

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.eng.hokudai.ac.jp/labo/tre/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.eng.hokudai.ac.jp/labo/tre/frame_j/biomaco_j_index.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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