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Novel pathway of coenzyme Q biosynthesis

Research Project

Project/Area Number 17H03806
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied biochemistry
Research InstitutionShimane University

Principal Investigator

Kawamukai Makoto  島根大学, 学術研究院農生命科学系, 教授 (70186138)

Co-Investigator(Kenkyū-buntansha) 村井 正俊  京都大学, 農学研究科, 准教授 (80543925)
戒能 智宏  島根大学, 学術研究院農生命科学系, 准教授 (90541706)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordscoenzyme Q / ubiquinone / S. pombe / fission yeast / PHB / PABA / isoprenoid / コエンザイムQ / ユビキノン / 分裂酵母 / coenzymeQ / mitochondria / S. pome / ミトコンドリア / 電子伝達系 / 抗酸化 / イソプレノド
Outline of Final Research Achievements

Coenzyme Q (CoQ, ubiquinone) is an essential component of the electron transport system in aerobic organisms. Human type CoQ10, which has 10 units of isoprene in its quinone structure, is especially valuable as a food supplement. Therefore, studying the biosynthesis of CoQ10 is important not only for increasing metabolic knowledge, but also for improving biotechnological production. Herein, we show that Schizosaccharomyces pombe utilizes p-aminobenzoate (PABA) in addition to p-hydroxybenzoate (PHB) as a precursor for CoQ10 synthesis. We explored compounds that affect the synthesis of CoQ10 and found benzoic acid inhibited CoQ biosynthesis without accumulation of apparent CoQ intermediates. This inhibition was counteracted by incubation with a 10-fold lower amount of PABA or PHB. Overexpression of PHB-polyprenyl transferase encoded by ppt1 (coq2) also overcame the inhibition of CoQ biosynthesis by benzoic acid.

Academic Significance and Societal Importance of the Research Achievements

CoQ10 は1974年から医薬品として、虚血性心不全、筋ジストロフィー、貧血等に効果があることで使用されていたが、2001年に食品として認可されてからは食品サプリメントとして、幅広く市場に普及している。CoQ10は人間の体内でも合成されているが、その量は加齢とともに減少することから、食品サプリメントとして補うと効果的である。最近の研究によりCoQ10の合成量が低下している患者は、ミトコンドリア脳筋症になり、重篤な症状を示すということが報告され、遺伝病との関連性が注目されている。そのような背景の基、酵母を用いてCoQ10の生合成を解明することは、病気の原因の解明にも繋がる重要な研究である。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] Organelle specific simultaneous Raman/GFP microspectroscopy for living cell toward physiochemical studies2020

    • Author(s)
      N. Wattanavichean, I. Nishida, M. Ando, M. Kawamukai, T. Yamamoto, H. Hamaguchi
    • Journal Title

      J. Biophotonics

      Volume: 13 Issue: 4 Pages: 1-6

    • DOI

      10.1002/jbio.201960163

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Benzoic acid inhibits Coenzyme Q biosynthesis in Schizosaccharomyces pombe2020

    • Author(s)
      Ikuhisa Nishida, Ryota Yanai, Yasuhiro Matsuo, Tomohiro Kaino, Makoto Kawamukai
    • Journal Title

      PloS One

      Volume: 15 Issue: 11 Pages: 1-21

    • DOI

      10.1371/journal.pone.0242616

    • NAID

      120007002148

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CoQ10 production in Schizosaccharomyces pombe is increased by reduction of glucose levels or deletion of pka12019

    • Author(s)
      Nishida I., Yokomi K., Hosono K., Hayashi K., Matsuo Y., Kaino T., Kawamukai M.
    • Journal Title

      Appl. Microbiol. Biotechnol.

      Volume: 103 Issue: 12 Pages: 4899-4915

    • DOI

      10.1007/s00253-019-09843-7

    • NAID

      120007002146

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studying anti-oxidative properties of inclusion complexes of α-lipoic acid with γ-cyclodextrin in single living fission yeast by confocal Raman microspectroscopy2018

    • Author(s)
      Noothalapati Hemanth、Ikarashi Ryo、Iwasaki Keita、Nishida Tatsuro、Kaino Tomohiro、Yoshikiyo Keisuke、Terao Keiji、Nakata Daisuke、Ikuta Naoko、Ando Masahiro、Hamaguchi Hiro-o、Kawamukai Makoto、Yamamoto Tatsuyuki
    • Journal Title

      Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

      Volume: 197 Pages: 237-243

    • DOI

      10.1016/j.saa.2018.02.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biosynthesis and applications of prenylquinones2018

    • Author(s)
      Kawamukai Makoto
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 6 Pages: 963-977

    • DOI

      10.1080/09168451.2018.1433020

    • NAID

      120006819039

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of respiratory growth defect of mutant deficient in mitochondrial phospholipase A1 by overexpression of genes involved in coenzyme Q synthesis in Saccharomyces cerevisiae2018

    • Author(s)
      Shiho Morisada、Ikuhisa Nishida、Makoto Kawamukai、Hiroyuki Horiuchi、Ryouichi Fukuda
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 9 Pages: 1633-1639

    • DOI

      10.1080/09168451.2018.1476124

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Schizosaccharomyces japonicus has low levels of CoQ10 synthesis, respiration deficiency, and efficient ethanol production at high temperature.2018

    • Author(s)
      Tomohiro Kaino, Kai Tonoko, Shiomi Mochizuki, Yuriko Takashima, Makoto Kawamukai
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 82 Issue: 6 Pages: 1031-1042

    • DOI

      10.1080/09168451.2017.1401914

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] コエンザイムQ10増産技術の開発2017

    • Author(s)
      戒能智宏、川向誠
    • Journal Title

      バイオインダストリー

      Volume: 34 Pages: 63-71

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Urea enhances cell lysis of Schizosaccharomyces pombe ura4 mutants.2017

    • Author(s)
      Kohei Nishino, Misaki Kushima, Tomohiro Kaino, Yasuhiro Matsuo, Makoto Kawamukai
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 81 Issue: 7 Pages: 1444-1451

    • DOI

      10.1080/09168451.2017.1303360

    • NAID

      120006819049

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 安息香酸は分裂酵母のコエンザイムQ生合成を顕著に阻害する2021

    • Author(s)
      西田 郁久、柳井 良太、松尾 安浩、戒能 智宏、川向 誠
    • Organizer
      日本農芸化学会202年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分裂酵母および出芽酵母のPos5がCoQ生合成に影響する2021

    • Author(s)
      西原 昇瑚、西田 郁久、柳井 良太、松尾 安浩、戒能 智宏、川向 誠
    • Organizer
      日本農芸化学会202年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分裂酵母Schizosaccharomyces pombeのCoQ生合成に関与するPos5の解析2020

    • Author(s)
      西原 昇瑚、西田 郁久、柳井 良太、戒能 智宏、川向 誠
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 安息香酸は分裂酵母のCoQ生合成を顕著に阻害する2020

    • Author(s)
      西田 郁久、戒能 智宏、松尾 安浩、川向 誠
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Biosynthesis of Coenzyme Q and its role in S. pombe and S. japonicus2019

    • Author(s)
      Kawamukai, M., Tonoko, K., Narahara, T., Nishida, I., Kaino, T
    • Organizer
      The 10th international fission yeast meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Coenzyme Q10 production in Schizosaccharomyces pombe is increased by reduction of glucose levels or deletion of pka1.2019

    • Author(s)
      Nishida, I., Yokomi, K., Hosono, K., Hayashi, K., Matsuo, Y., Kaino, T., Kawamukai, M
    • Organizer
      The 10th international fission yeast meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 分裂酵母S. japonicusの CoQ 欠損株は,最少培地でも生育し,硫化水素を発生しない2019

    • Author(s)
      楢原拓之,渡子 開,西田郁久,戒能智宏,川向 誠
    • Organizer
      日本農芸化学会 2019 年度西日本・中四国支部合同沖縄大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] コエンザイムQの生合成と生産2019

    • Author(s)
      川向 誠
    • Organizer
      第29回イソプレノイド研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] コエンザイムQ生合成の新規遺伝子2019

    • Author(s)
      川向 誠
    • Organizer
      日本農芸化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] A novel gene involved in CoQ biosynthesis in fission yeast2018

    • Author(s)
      Makoto Kawamukai
    • Organizer
      The 9th conference of the international Coenzyme Q10 association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Coenzyme Q biosynthesis and application in yeasts and plants2018

    • Author(s)
      Makoto Kawamukai
    • Organizer
      The 23rd international symposium on plant lipids
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分裂酵母のCoQ生合成に関わる新規遺伝子2018

    • Author(s)
      西田郁久、戒能智宏、川向誠
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] コエンザイムQ10と老化2018

    • Author(s)
      川向誠
    • Organizer
      日本農芸化学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 新規なコエンザイムQ生合成遺伝子の発見2017

    • Author(s)
      西田郁久、大森夕貴、柳井良太、松尾安浩、戒能智宏、川向誠
    • Organizer
      第27回イソプレノイド研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] コエンザイムQ10の生合成に関わる新規因子の発見2017

    • Author(s)
      西田郁久、柳井良太、松尾安浩、戒能智宏、川向誠
    • Organizer
      日本農芸化学会関西・中四国・西日本支部2017年度合同大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Investigation of coenzyme Q species in naturally isolated yeast2017

    • Author(s)
      Jomkwan Jumpathong ,Ikuhisa Nishida,Kohei Nishino,Yasuhiro Matsuo,Tomohiro Kaino, Makoto Kawamukai
    • Organizer
      日本農芸化学会関西・中四国・西日本支部2017年度合同大会
    • Related Report
      2017 Annual Research Report
  • [Book] 酵母によるコエンザイムQ10の生産2018

    • Author(s)
      戒能智宏、川向誠
    • Total Pages
      264
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313177
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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