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Studies of bio-regulation with D-amino acids and its application

Research Project

Project/Area Number 16H04908
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Yoshimura Tohru  名古屋大学, 生命農学研究科, 教授 (70182821)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
KeywordsD-アミノ酸 / D-セリン / セリンラセマーゼ / D-セリンデヒドラターゼ / 腎疾患マーカー / D-アスパラギン酸 / D-アミノ酸トランスアミナーゼ / 酵素 / D-アミノ酸 / バイオテクノロジー / 腎障害マーカー / 細胞性粘菌 / 生理活性 / 分析
Outline of Final Research Achievements

The goal of this study is to clarify the metabolism and physiological functions of D-amino acids, and their application to various research tools. The following studies were conducted. 1) Serine racemase, which is responsible for the biosynthesis of D-Ser, a co-agonist of NMDA receptor, was confirmed to catalyze the D-serine dehydration. 2) An unknown D-amino acid was found in an edible mushroom, Hypsizygus marmoreus, and identified as D-2-amino-3,4-dihydroxy-butanoic acid. (3) Urinary D-Ser concentrations of renal disease patients and healthy subjects were analyzed. Ratio of the urinary D-Ser concentration to that of urinary creatinine was suggested to serve as a biomarker of renal disorder. (4) Functional cloning system of the genes encoding D-amino acid synthesizing enzymes was constructed with E. coli mutant lacking alanine racemase and glutamate racemase genes.

Academic Significance and Societal Importance of the Research Achievements

D-アミノ酸の生理機能が注目されている。例えば D-Serは記憶や学習などの脳機能に、D-Aspは脳ホルモンの分泌などに関与する。本研究では D-アミノ酸の機能や代謝の解明、様々な研究ツールへの応用を試みた。具体的には、D-Ser合成を担うセリンラセマーゼがD-Serの分解にも働くこと、ブナシメジに新奇D-アミノ酸、D-2-amino-3,4-dihydroxy-butanoic acidが存在すること、尿中のD-Serとクレアチニンの濃度比が腎疾患マーカーへ応用可能であることを示した。また D-アミノ酸研究の強力なツールとなるD-アミノ酸生合成酵素遺伝子スクリーニング系を構築した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Conserved Pyridoxal 5'-Phosphate Binding Protein YggS Impacts Amino Acid Metabolism through Pyridoxine 5'-Phosphate in Escherichia coli.2019

    • Author(s)
      Ito T, Yamamoto K, Hori R, Yamauchi A, Downs DM, Hemmi H, Yoshimura T.
    • Journal Title

      Appl Environ Microbiol.

      Volume: 11 Issue: 11

    • DOI

      10.1128/aem.00430-19

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] D-Serine Metabolism and Its Importance in Development of Dictyostelium discoideum2018

    • Author(s)
      Ito T, Hamauchi N, Hagi T, Morohashi N, Hemmi H, Sato YG, Saito T, Yoshimura T.
    • Journal Title

      Front Microbiol

      Volume: 9 Pages: 784-784

    • DOI

      10.3389/fmicb.2018.00784

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors2018

    • Author(s)
      Iwakawa H, Makabe S, Ito T, Yoshimura T, Watanabe H.
    • Journal Title

      Biomarkers

      Volume: Oct 23 Issue: 2 Pages: 1-7

    • DOI

      10.1080/1354750x.2018.1528632

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of Ophthalmic Acid Using Engineered Escherichia coli2018

    • Author(s)
      Ito T, Tokoro M, Hori R, Hemmi H, Yoshimura T
    • Journal Title

      Appl Environ Microbiol

      Volume: 84 Issue: 7 Pages: 02806-02817

    • DOI

      10.1128/aem.02806-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ピリドキサール5’-リン酸に依存する細菌の転写制御因子GabR2018

    • Author(s)
      吉村 徹
    • Journal Title

      ビタミン

      Volume: 92 Pages: 86-89

    • NAID

      130007605227

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Occurrence of the (2R,3S)-Isomer of 2-Amino-3,4-dihydroxybutanoic Acid in the Mushroom Hypsizygus marmoreus.2017

    • Author(s)
      Ito T, Yu Z, Yoshino I, Hirozawa Y, Yamamoto K, Shinoda K, Watanabe A, Hemmi H, Asada Y, Yoshimura T.
    • Journal Title

      J Agric Food Chem.

      Volume: 65 Issue: 30 Pages: 6131-6139

    • DOI

      10.1021/acs.jafc.7b01893

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serine racemase is involved in D-aspartate biosynthesis.2016

    • Author(s)
      Ito T, Hayashida M, Kobayashi S, Muto N, Hayashi A, Yoshimura T, Mori H.
    • Journal Title

      J. Biochem.

      Volume: 160 Pages: 345-353

    • NAID

      40021050460

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ophthalmic acid accumulation in an Escherichia coli mutant lacking the conserved pyridoxal 5'-phosphate-binding protein YggS.2016

    • Author(s)
      Ito T, Yamauchi A, Hemmi H, Yoshimura T.
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 122 Issue: 6 Pages: 689-693

    • DOI

      10.1016/j.jbiosc.2016.06.010

    • NAID

      120005981280

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] D-アミノ酸アミノトランスフェラーゼを用いたD-アミノ酸生合成酵素遺伝子のスクリーニング2019

    • Author(s)
      那須 涼麻、伊藤 智和、武藤 菜摘、坂神 晴菜、邊見 久、森 寿、吉村 徹
    • Organizer
      2019年度日本農芸化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Eukaryotic D-Serine Dehydratase and its Application to D-Serine Assay2018

    • Author(s)
      Tohru Yoshimura, Tomokazu Ito, Hisashi Hemmi
    • Organizer
      AC21 Joint mini‐symposium “Agro‐Industry Research for well‐being”
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] D-アミノ酸合成酵素の同定を目的としたファンクショナルクローニング系の開発2018

    • Author(s)
      伊藤智和,武藤菜摘,邊見久,吉村徹
    • Organizer
      日本ビタミン学会第 70 回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規D-アミノ酸生合成酵素のスクリーニング系の確立2018

    • Author(s)
      那須 涼麻、伊藤 智和、邊見 久、森 寿、吉村 徹
    • Organizer
      第14回D-アミノ酸研究会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] E.coli由来PLP結合タンパク質YggSの生理機能解明2018

    • Author(s)
      堀 蘭、伊藤 智和、邊見 久、吉村 徹
    • Organizer
      酵素補酵素研究会2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] YggS/PROSCファミリータンパク質のアミノ酸代謝制御機構の解析2018

    • Author(s)
      山本 佳奈, 伊藤 智和, 邊見 久, 吉村 徹
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 微生物酵素のD-アミノ酸研究への応用2018

    • Author(s)
      吉村 徹
    • Organizer
      応用生命化学研究センター第9回公開シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Ophthalmic acid production by E. coli yggS mutant2017

    • Author(s)
      Tohru Yoshimura, Ayako Yamauchi, Maiko Tokoro, Hisashi Hemmi, Tomokazu Ito
    • Organizer
      Italy-Japan Joint Symposium “New Trends in Enzyme and Microbial Science in the Translational Biology Era”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Production of opthalmic acid with an E. coli mutant lacking the conserved pyridoxal protein YggS2017

    • Author(s)
      Tohru Yoshimura, Ayako Yamauchi, Maiko Tokoro, Hisashi Hemmi, Tomokazu Ito
    • Organizer
      19th Japan-German Workshop on Enzyme Technology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional regulator of Brevibacillus brevis D-alanine: D-alanine ligase gene2017

    • Author(s)
      Tohru Yoshimura, Takashi Takenaka, Tomokazu Ito, Ikuko Miyahara, Hisashi Hemmi
    • Organizer
      International Conference of D-Amino Acid Research(IDAR2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reaction mechanism of eukaryotic serine racemase catalyzing both racemization and dehydration of D-,L-serine2016

    • Author(s)
      Tohru Yoshimura
    • Organizer
      The Fifth International Conference on Cofactors & Active Enzyme Molecule 2016(ICC05-AEM2016)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 真核生物におけるD-アミノ酸の機能とその代謝関連酵素2016

    • Author(s)
      吉村徹
    • Organizer
      第12回D-アミノ酸研究会学術講演会・日本農芸化学会中四国支部合同シンポジウム「環境・ひと・微生物」
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] D-アミノ酸の機能と代謝関連酵素2016

    • Author(s)
      吉村徹
    • Organizer
      日本農芸化学会平成28年度関西支部大会(第496回講演会)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ブナシメジの新奇D-アミノ酸2016

    • Author(s)
      吉村徹
    • Organizer
      第446回ビタミンB研究協議会
    • Related Report
      2016 Annual Research Report
  • [Book] D-Amino acids Physiology, Metabolism, and Application2016

    • Author(s)
      Yoshimura T 他(Yoshimura, Tohru, Nishikawa, Toru, Homma, Hiroshi (Eds.)
    • Total Pages
      357
    • Publisher
      Springer
    • ISBN
      4431560750
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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