| Project/Area Number |
18K14377
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38020:Applied microbiology-related
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| Research Institution | Niigata University (2020)
Shimane University (2018-2019) |
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Principal Investigator |
Nishida Ikuhisa 新潟大学, 日本酒学センター, 特任助教 (20784531)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | コエンザイムQ / ユビキノン / 安息香酸 / タンパク質キナーゼA / 炭素源 / 分裂酵母 / p-アミノ安息香酸(PABA) / p-ヒドロキシ安息香酸(PHB) / p-アミノ安息香酸 / p-ヒドロキシ安息香酸 / Coq12 / コエンザイムQ10 / ミトコンドリア / 生合成 / Pka1 / 阻害剤 / PKA1 / グルコース |
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| Outline of Final Research Achievements |
Coenzyme Q (CoQ) is an essential component of the electron transport system that produces ATP in nearly all living cells. In this study, we tried to identify novel CoQ biosynthetic pathways, and the biosynthetic regulators (genes and compounds) in Schizosaccharomyces pombe. First, it was revealed that Coq12 is a novel factor involved in the biosynthesis of p-hydroxybenzoate (PHB) and quinone frame of CoQ. Next, we focused on upstream of CoQ biosynthesis and showed that S. pombe utilizes p-aminobenzoate (PABA) in addition to PHB as a precursor for CoQ10 synthesis. We explored compounds that affect the synthesis of CoQ10 and found that benzoic acid at a concentration of 5 μg/mL or higher significantly inhibited CoQ biosynthesis without accumulation of apparent CoQ intermediates. Third, we tried to find novel regulators for CoQ production, and demonstrated that carbon source, growth phase, and the cAMP-signaling pathway are important factors in CoQ10 production in S. pombe.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では分裂酵母におけるCoQの代謝調節に関わる新規因子を多数明らかにした。CoQ生合成は生物界に広く保存されているため、本研究の成果は分裂酵母に留まらず多種生物におけるCoQを介したエネルギー産生・抗酸化能の付与などに関する全貌解明への一助となる。また、CoQの欠乏と関連が深いミトコンドリア病、パーキンソン病、心臓病、高血圧、線維筋痛症等の疾患の治療や予防に繋げられる可能性が考えられる。さらに、本研究で同定した因子の活用により、実用酵母を用いたCoQ10の発酵生産性の更なる向上に期待できる。加えて、CoQの新たな代謝調節機構を活用することで、新規な物質生産・発酵生産系の構築にも期待できる。
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