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Analysis of a physiological role and anti-asthmatic activity of the chitinase inhibior allosamidin

Research Project

Project/Area Number 17380072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

SAKUDA Shohei  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor (80192087)

Co-Investigator(Kenkyū-buntansha) INOUE Hiromasa  Kyushu University, Hospital, Lecturer (30264039)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥14,130,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥630,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2005: ¥9,500,000 (Direct Cost: ¥9,500,000)
Keywordsenzyme inhibitor / chitin / chitinase / asthma / physiological activity / secondary metabolite / allosamidin / Streptomyces
Research Abstract

Allosamidin, a secondary metabolite of Streptomyces, inhibits family 18 chitinases which are widely present in nature Allosamidin has been used to study the physiological role of chitinases in a variety of organisms. Recently, two novel biological activities of allosamidin were found. One is the anti-asthmatic activity toward mammals. The other is the chitinase-production promoting activity toward its producing bacterium. In this project, we investigated the molecular mechanism of allosamidin in each of the biological activities.
Demethylallosamidin, an allosamidin derivative, was found to show much stronger anti-asthmatic activity than allosamidin. Photoaffinity and biotinylated probes of allosamidin and demethylallosamidin were prepared to detect allosamidins-binding proteins in the lung of asthma model mouse. Ym1, a chitinase-like protein, was identified as the main specific allosamidin-binding protein. Affinity of allosamidin and demethylallosamidin for Ym1 was very high (K_D value is around 10^<-8> M). Demthylallosamidin showed stronger binding affinity for Ym1 than allosamidin. Work to clarify the physiological function of Ym1 by using allosamidins is now in progress.
Allosamidin promoted chitinase production of an allosamidin-producing Streptomyces in a chitin medium at low concentrations such as 60 nM. The chitinase gene whose expression is enhanced by allosamidin was shown to have a direct repeat moiety in the promoter region and two genes encoding a two-component regulatory system at the 5''-upstream region. Gene disruption experiment showed that expression of the chitinase gene is induced by N, N''-diacetylchitobiose and allosamidin can enhance the expression through the two-component regulatory system. Allosamidin promotes chitinase production of Streptomyces species widely. It is important to investigate the physiological function of allosamidin in a chitin-rich environment such as in soils.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (43 results)

All 2008 2007 2006 Other

All Journal Article (15 results) (of which Peer Reviewed: 5 results) Presentation (24 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Chtinase Inhibitor allosamidin promotes chitinase production of Streptomyces2008

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Keiko Furihata, Katsushiro Miyamoto, Hiroshi Tsujibo, Takeshi Watanabe, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      International Journal of Biological Maclomolecule (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A Thermodynamic analysis of allosamidin binding to a family 18 chitinase2007

    • Author(s)
      Henning Cederkvist, Silie Saua, Vigdis Karlsen, Shohei Sakuda, Vincent Eijsink, Morten Sφrlie
    • Journal Title

      Biochemistry 46

      Pages: 12347-12354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] キチナ-ゼ生産促進物質として機能するキチナ-ゼ阻害物質アロサミジン2007

    • Author(s)
      鈴木茂雄、作田庄平
    • Journal Title

      化学と生物 45

      Pages: 843-850

    • NAID

      10019973575

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Vincent Eijsink, Morten Serlie A Thermodynamic analysis of allosamidin binding to a family 18 chitinase2007

    • Author(s)
      Henning Cederkvist, Silie Saua, Vigdis Karlsen, Shohei Sakuda
    • Journal Title

      Biochemistry 46(43)

      Pages: 12347-12354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Allosamidin a chitinase inhibitor, functions as a signal molecule for chitinase production in its producing Streptomyces2007

    • Author(s)
      Shigeo Suzuki, Shohei Sakuda
    • Journal Title

      Kagakutoseibutsu 45(12)

      Pages: 843-850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] キチナーゼ生産促進物質として機能するキチナーゼ阻害物質アロサミジン2007

    • Author(s)
      鈴木 茂雄、作田 庄平
    • Journal Title

      化学と生物 45

      Pages: 843-850

    • NAID

      10019973575

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. I. Analysis of the chitinase whose production is promoted by allosamidin and growth accelerating activity of allosamidin2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      Journal of Antibiotics 59

      Pages: 402-409

    • NAID

      10017649455

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. II. Mechanism for regulation of chitinase production by allosamidin through a two-component regulatory system2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      Journal of Antibiotics 59

      Pages: 410-417

    • NAID

      10017649473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. I. Analysis of the chitinase whose production is promoted by allosamidin and growth accelerating activity of allosamidin2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      J. Antibiotic 59(7)

      Pages: 402-409

    • NAID

      10017649455

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. II. Mechanism for regulation of chitinase production by allosamidin through a two-component regulatory system2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      J. Antibiotic 59(7)

      Pages: 410-417

    • NAID

      10017649473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. I. Analysis of the chitinase whose production is promoted by allosamidin and growth accelerating activity of allosamidin.2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      Journal of Antibiotics 59・7

      Pages: 402-409

    • NAID

      10017649455

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces. II. Mechanism for regulation of chitinase production by allosamidin through a two-component regulatory system.2006

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      Journal of Antibiotics 59・7

      Pages: 410-417

    • NAID

      10017649473

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chtinase inhibitor allosamidin promotes chitinase production of Streptomyces generally

    • Author(s)
      Shigeo Suzuki, Eiyu Nakanishi, Keiko Furihata, Katsushiro Miyamoto, Hiroshi Tsujibo, Takeshi Watanabe, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      Int. J. Biol. Macromol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Chitinase inhibitors and its significance in biology In Binomium Chitin-Chitinase : Emerging issue

    • Author(s)
      Shohei Sakuda
    • Journal Title

      Nova Science Publishers, Inc (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Chtinase inhibitor allosamidin promotes chitinase production of Streptomyces generally

    • Author(s)
      Shigeo, Suzuki, Eiyu Nakanishi, Keiko Furihata, Katsushiro Miyamoto, Hiroshi Tsujibo, Takeshi Watanabe, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Journal Title

      International Journal of Biological Macromolecules(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 微生物二次代謝産物の生物活性と生理活性2008

    • Author(s)
      作田庄平
    • Organizer
      日本農芸化学会2008年度大会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Biological and physiological activities of microbial Secondary metabolites2008

    • Author(s)
      Shohei Sakuda
    • Organizer
      Annual meeting of JSBBA 2007
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-03-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 抗喘息作用物質アロサミジン類の作用機構解析2008

    • Author(s)
      佐藤陽亮、松本崇史、井上博雅、長澤寛道、作田庄平
    • Organizer
      日本農芸化学会2008年度大会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of the mode of action of allosamidins, anti-asthmatic compounds2008

    • Author(s)
      Yosuke Sato, Takafumi Matsumoto, Hiromasa Inoue, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      Annual meeting of JSBBA 2008
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジンのキチナーゼ生産促進機構と普遍性2007

    • Author(s)
      鈴木茂雄、田川直史、菊池直也、吉成知也、宮本勝城、辻坊 裕、渡邉剛志、大西康夫、堀之内末治、長澤寛道、作田庄平
    • Organizer
      第21回キチン・キトサンシンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-07-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of the mode of action of allosamidins for.anti-asthmatic activity2007

    • Author(s)
      Yosuke Sato, Shigeo Suzuki, Takafumi Matsumoto, Hiromasa Inoue, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      21st Chitin and Chitosan Symposium
    • Place of Presentation
      Kobe
    • Year and Date
      2007-07-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of chitinase-production promoting activity of allosamidin and its generality2007

    • Author(s)
      Shigeo Suzuki, Naofumi Tagawa, Naoya Kikuchi, Tomoya Yoshinari, Katsushiro Miyamoto, Hiroshi Tsujibo, Takeshi Watanabe, Yasuo Ohnishi, SueharuHorinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      21st Chitin and Chitosan Symposium
    • Place of Presentation
      Kobe
    • Year and Date
      2007-07-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジン類の抗喘息作用の機能解析2007

    • Author(s)
      佐藤陽亮、鈴木茂雄、松本崇史、井上博雅、長澤寛道、作田庄平
    • Organizer
      第21回キチン・キトサンシンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-07-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジンをシグナルとする放線菌のキチン代謝活性化機構2007

    • Author(s)
      作田庄平、鈴木茂雄、大西康夫、堀之内末治、長澤寛道
    • Organizer
      日本農芸化学会2007年度大会
    • Place of Presentation
      東京
    • Year and Date
      2007-03-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism for chitin metabolism activation by allosamidin as a signal molecule2007

    • Author(s)
      Shohei Sakuda, Shigeo Suzuki, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa
    • Organizer
      Annual meeting of JSBBA 2007
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-03-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジンによるキチナーゼ生産促進の分子機構に関する研究(その4)2007

    • Author(s)
      鈴木茂雄、大西康夫、堀之内末治、宮本勝城、辻坊 裕、降旗桂子、長澤寛道、作田庄平
    • Organizer
      日本農芸化学会2007年度大会
    • Place of Presentation
      東京
    • Year and Date
      2007-03-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジン誘導体の抗喘息作用活性2007

    • Author(s)
      佐藤陽亮、鈴木茂雄、松本崇史、井上博雅、長澤寛道、作田庄平
    • Organizer
      日本農芸化学会2007年度大会
    • Place of Presentation
      東京
    • Year and Date
      2007-03-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Studies on the molecular mechanism for chitinase-production promoting activity of allosamidin (part 4)2007

    • Author(s)
      Shigeo Suzuki, Yasuo Ohnishi,. Sueharu Horinouchi, Katsushiro Miyamoto, Hiroshi Tsujibo, Keiko Furihata, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      Annual meeting of JSBBA 2007
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-03-25
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Anti-asthmatic activity of allosamidin derivatives2007

    • Author(s)
      Yosuke Sato, Shigeo Suzuki, Takafumi Matsumoto, Hiromasa Inoue, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      Annual meeting of JSBBA 2007
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-03-25
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] シグナル分子として機能するアロサミジンの作用機構解析2006

    • Author(s)
      鈴木茂雄、大西康夫、堀之内末治、長澤寛道、作田庄平
    • Organizer
      第20回キチン・キトサンシンポジウム
    • Place of Presentation
      福井
    • Year and Date
      2006-08-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of the function of allosamidin which acts as a signal molecule2006

    • Author(s)
      Shigeo Suzuki, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      20th Chitin and Chitosan Symposium
    • Place of Presentation
      Fukui
    • Year and Date
      2006-08-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] マウス酸性キチナーゼに対するアロサミジンの阻害活性2006

    • Author(s)
      佐藤陽亮、鈴木茂雄、松本崇史、井上博雅、長澤寛道、作田庄平
    • Organizer
      第20回キチン・キトサンシンポジウム
    • Place of Presentation
      福井
    • Year and Date
      2006-08-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Inhibitory activity of allosamidin toward mouse acidic mammalian chitinase2006

    • Author(s)
      Yosuke Sato, Shigeo Suzuki, Takafumi Matsumoto, Hiromasa Inoue, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      20th Chitin and Chitosan Symposium
    • Place of Presentation
      Fukui
    • Year and Date
      2006-08-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジンによるキチナーゼ生産促進の分子機構に関する研究2006

    • Author(s)
      鈴木茂雄、河内 隆、作田庄平、大西康夫、堀之内末治、長澤寛道
    • Organizer
      日本放線菌学会2006年度大会
    • Place of Presentation
      千葉
    • Year and Date
      2006-07-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Studies on the molecular mechanism for chitinase-production promoting activity of allosamidin2006

    • Author(s)
      Shigeo Suzuki, Ryu Kawachi, Shohei Sakuda, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa
    • Organizer
      Annual meeting of the Society for Actinomycetes Japan 2006
    • Place of Presentation
      Chiba
    • Year and Date
      2006-07-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アロサミジンによるキチナーゼ生産促進の分子機構に関する研究(その3)2006

    • Author(s)
      鈴木茂雄、作田庄平、大西康夫、堀之内末治、長澤寛道
    • Organizer
      日本農芸化学会2006年度大会
    • Place of Presentation
      京都
    • Year and Date
      2006-03-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Studies on the molecular mechanism for chitinase-production promoting activity of allosamidin (part 3)2006

    • Author(s)
      Shigeo Suzuki, Shohei Sakuda, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa
    • Organizer
      Annual meeting of JSBBA 2006
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing Streptomyces2006

    • Author(s)
      Suzuki Shigeo, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      10th International Conference on Chtin & Chitosan
    • Place of Presentation
      Montpellier (France)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Allosamidin is a signal molecule for chitinase production in its producing Streptomyces2006

    • Author(s)
      Suzuki Shigeo, Eiyu Nakanishi, Tsuyoshi Ohira, Ryu Kawachi, Yasuo Ohnishi, Sueharu Horinouchi, Hiromichi Nagasawa, Shohei Sakuda
    • Organizer
      10th International Conference on Chitin & Chitosan, Chitinase inhibitor
    • Place of Presentation
      Montpellier
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Chitinase inhibitors and its significance ni biology In Binomium Chitin-Ciitinase: Emerging issues Edited by Salvatole Musume2008

    • Author(s)
      Shohei Sakuda
    • Publisher
      Nova Science Publishers, Inc(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] "Chitinase inhibitors and its significance in biology" in Biononium Chitin-Chitinase: Emerging issues" edited by Salvatore Musumeci and Maurizio G. Paletti (掲載確定)

    • Author(s)
      Shohei Sakuda
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2007 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://park.itc.u-tokyo.ac.jp/seiyu/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://park.itc.u-tokyo.ac.jp/seiyu/

    • Related Report
      2007 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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