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Studies on a new biosynthetic pathway for menaquinone (vitamin K)

Research Project

Project/Area Number 17380075
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionTokyo University of Agriculture

Principal Investigator

SETO Haruo  Tokyo University of Agriculture, Faculty of Applied Bioscience, Professor (10013335)

Co-Investigator(Kenkyū-buntansha) SUE Masayuki  Tokyo University of Agriculture, Faculty of Applied Bioscience, 講師 (10328544)
DAIRI Toru  Toyama Prefectural University, Biotechnology Research Center, Associate Professor (70264679)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥13,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsmenauumone / vitamin K / Streptomyces coelicolor / biosynthetic intermediates / blocked mutants / Helicobacter pylori / Cambylobacter jejunj / Streptomyces sp. CL190 / 生合成 / メナキノン生合成経路 / ホスホエノールピルビン酸 / エリスロース
Research Abstract

We found that some pathogenic bacteria including Helicobacter pylori and Campylobacter jejuniutilized a new biosynthetic pathway for menaquinone. This pathway is also present in the genus Streptomyces and branches from the well known menaquinone biosynthetic pathway at chorismate. Since this pathway does not present in human, its inhibitors are expected to be useful as antibacterial substances. In order to reveal the details of this pathway, we carried out the following experiments.
1. At the onset of the experiments, we established unequivocal assignment of 13C-N1VIR spectrum of menaquinone.
2. Labeling experiments using glucoses labeled by^<13>C at different position proved that menaquinone was formed from erythrose, phosphoenolpyruvate and two different C_2 units originating from C5-C6 of glucose.
3. Several kinds of blocked mutants of Streptomyces coelicolor that required menaquinone for their growth were prepared.
4. Based on the results obtained by labeling experiments, 1,4-naphthoquinone-6-carboxylic acid was assumed to be a biosynthetic intermediate of the new pathway. Therefore, we prepared this acid by oxidation of naphthalene-2-carboxylic acid by using Ce(SO_4)_2. This compound enabled the growth of a menaquinone auxotroph of S coelicolor indicating that the synthetic compound is a true intermediate of the new pathway.
5. By detailed investigation of metabolites accumulated by mutants of S coelicolor a nucleoside compound, futalosine, was isolated. This compound consisted of inosine and a m-substituted benzoic acid derivative, and had been isolated from another strain of Streptomyces as an antitumor substance. This compound was proved to be a biosynthetic intermediate of the new pathway, since it supported the growth of some menaquinone auxotrophs of S coelicolor.
6. By utilizing other menaquinone auxotrophs of S coelicolor, several intermediates after futalosine were identified.

Report

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

    (8 results)

All 2008 2007

All Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Studies on a new biosynthetic pathway for menaquinone2008

    • Author(s)
      H. Seto, Y. Jinnai, T. Dairi
    • Journal Title

      J.Arner.Chem.Soc. 130

      Pages: 5614-5615

    • 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] Studies on a new biosynthetic pathway for menaquinone2008

    • Author(s)
      H., Seto, Y., Jinnai, T., Hiratsuka, M., Fukawa, K., Furihata, N., Itoh, T., Dairi
    • Journal Title

      J. Amer. Chem. Soc 130

      Pages: 5614-5615

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Studies on a new biosynthetic pathway for menaquinone2008

    • Author(s)
      H. Seto, Y. Jinnai, T. Dairi
    • Journal Title

      J. Amer. Chem. Soc. 130

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規メナキノン生合成経路に関する研究2008

    • Author(s)
      府川 美和子、瀬戸 治男、大利 徹
    • Organizer
      日本農芸化学会
    • Place of Presentation
      名古屋市名城大学
    • Year and Date
      2008-03-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Studies on a new biosynthetic pathway for menaquinone2008

    • Author(s)
      M., Fukawa, Y., Jinnai, T., Hiratsuka, K., Furihata, S., Itoh, T., Dairi
    • Organizer
      National Meeting of Japan Society for Bioscience, Biotechnology, and Agrochemistry
    • Place of Presentation
      Meijo University, Nagoya
    • Year and Date
      2008-03-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 新規メナキノン生合成経路に関する研究2008

    • Author(s)
      府川美和子、瀬戸治男、大利 徹
    • Organizer
      日本農芸化学会
    • Place of Presentation
      名古屋名城大学
    • Year and Date
      2008-03-28
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許2007

    • Inventor(s)
      瀬戸 治男、大利 徹
    • Industrial Property Rights Holder
      株式会社ADEKA
    • Industrial Property Number
      2007-147510
    • Filing Date
      2007-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許2007

    • Inventor(s)
      瀬戸治男、大利 徹
    • Industrial Property Rights Holder
      株式会社ADEKA
    • Patent Publication Number
      2008-011854
    • Filing Date
      2007-06-01
    • Related Report
      2007 Annual Research Report

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

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