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Biomodulation with D-amino acids: molecular mechanism and application

Research Project

Project/Area Number 25292059
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
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)

Co-Investigator(Kenkyū-buntansha) HEMMI Hisashi  名古屋大学, 大学院生命農学研究科, 准教授 (60302189)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
KeywordsD-アミノ酸 / D-セリン / D-アスパラギン酸 / セリンラセマーゼ / D-セリンデヒドラターゼ / D-アスパラギン酸 / D-セリンデヒドラターゼ / D-アミノ酸スパラギン酸 / ビタミンB6 / 細胞性粘菌 / アスパラギン酸ラセマーゼ / ピリドキサルリン酸
Outline of Final Research Achievements

In the current studies, we intended to clarify the molecular bases of the physiological functions of D-amino acids, especially D-Ser and D-Asp. We clarified the reaction mechanism of D-Ser metabolizing enzymes、serine racemase and D-serine dehydratase with focusing on the elimination of the hydroxyl group of substrate. We examined the role of D-Ser and serine racemase in the cellular slime mold, Dictyostelium discoideum, and found that serine racemase probably regulates L-serine concentration. We tried to clarify the synthetic enzyme of D-Asp in mammals, and found that Got1l1 is not an aspartate racemase but a L-glutamate transaminase. We tried to improve the sensitivity of our enzymatic D-Ser assay system, and succeeded to increase it ten times. We attempted to regulate the brain D-Ser concentration with PEGylated D-serine dehydratase. We also studied the protein structure recognizing D-amino acids.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (31 results)

All 2016 2015 2014 2013

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 5 results,  Open Access: 1 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 12 results)

  • [Journal Article] A New Member of MocR/GabR-type PLP-Binding Regulator of D-Alanyl-D-Alanine Ligase in Brevibacillus brevis.2015

    • Author(s)
      Takenaka T., Ito T., Miyahara I., Hemmi H., Yoshimura T.
    • Journal Title

      FEBS J.

      Volume: 282 Issue: 21 Pages: 4201-4217

    • DOI

      10.1111/febs.13415

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of the aminotransferase domain in Bacillus subtilis GabR, a pyridoxal 5'-phosphate-dependent transcriptional regulator2015

    • Author(s)
      Okuda K., Kato S., Ito T., Shiraki S., Kawase Y., Goto M., Kawashima S., Hemmi H., Fukada H., Yoshimura T
    • Journal Title

      Molecular Microbiology

      Volume: 95 Issue: 2 Pages: 245-257

    • DOI

      10.1111/mmi.12861

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PEGylated D-Serine Dehydratase as a D-Serine Reucing Agent2015

    • Author(s)
      Ito T., Takada H., Isobe K., Suzuki M., Kitaura Y., Hemmi H., Matsuda T., Sasabe J., Yoshimura T.
    • Journal Title

      Journal of Parmacetuical and Biomedical Analysis

      Volume: in press Pages: 34-39

    • DOI

      10.1016/j.jpba.2014.12.044

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Domain characterization of Bacillus subtilis GabR, a pyridoxal 5′-phosphate-dependent transcriptional regulator2015

    • Author(s)
      Okuda K, Ito T, Goto M, Takenaka T, Hemmi H, Yoshimura T
    • Journal Title

      J. Biochem.

      Volume: to be assigned

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Is D-aspartate produced by glutamic-oxaloacetic transaminase -1 like 1(Got1l1), a putative aspartate racemase?2015

    • Author(s)
      Tanaka-Hayashi A, Hayashi S, Inoue R, Ito T, Konno K, Yoshida T, Watanabe M, Yoshimura T, Mori H
    • Journal Title

      Amino Acids

      Volume: 47 Issue: 1 Pages: 79-86

    • DOI

      10.1007/s00726-014-1847-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enzyme assay for pyridoxal 5'-phosphate by apo-D-amino acid aminotransferase2015

    • Author(s)
      Ota H, Mushiga M, Yoshimura T, Yoshimune K
    • Journal Title

      J. Biosci. Bioeng.

      Volume: to be assigned Issue: 1 Pages: 117-119

    • DOI

      10.1016/j.jbiosc.2014.12.006

    • NAID

      110009973295

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reaction mechanism of Zn2+-dependent D-serine dehydratase: role of a conserved tyrosine residue interacting with pyridine ring nitrogen of pyridoxal 5'-phosphate2014

    • Author(s)
      Ito T., Matsuoka M., Koga K., Hemmi H., Yoshimura T.
    • Journal Title

      Journal of Biochemistry

      Volume: 156 Issue: 3 Pages: 173-180

    • DOI

      10.1093/jb/mvu035

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Conserved pyridoxal protein that regulates Ile and Val metabolism.2013

    • Author(s)
      Ito T, Iimori J, Takayama S, Moriyama A, Yamauchi A, Hemmi H, Yoshimura T.
    • Journal Title

      J Bacteriol.

      Volume: 195 Issue: 24 Pages: 5439-5449

    • DOI

      10.1128/jb.00593-13

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規バイオマーカーとしての D-アミノ酸とその酵素定量法2016

    • Author(s)
      吉村 徹、邊見 久、伊藤智和
    • Organizer
      日本農芸化学会 2016年度大会シンポジウム
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Physiological function and metabolizing enzymes of D-amino acids2015

    • Author(s)
      Tohru Yoshimura, Hisashi Hemmi, Tomokazu Ito
    • Organizer
      2015 International Symposium on Agricultural Biotechnology
    • Place of Presentation
      Dong-A University
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] D-セリン分解の生物学と酵素学2015

    • Author(s)
      吉村 徹
    • Organizer
      日本アミノ酸学会第9回学術大会
    • Place of Presentation
      滋賀県立大学
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Properties of GabR, a pyridoxal 5’-phosphate-dependent transcriptional regulator of Bacillus subtilis, and alteration of its ligand specificity2015

    • Author(s)
      Tohru Yoshimura, Keita Okuda, Shiro Kato, Masaru Goto, Hisashi Hemmi, Harumi Fukada, Tomokzazu Ito
    • Organizer
      18th Japanese-German Workshop Enzyme Technology
    • Place of Presentation
      Kyoto University
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 真核生物型セリンラセマーゼが触媒するセリンデヒドレーション反応の機構2015

    • Author(s)
      吉村 徹、伊藤智和、松岡 舞、邊見久
    • Organizer
      第11回D-アミノ酸学会学術講演会
    • Place of Presentation
      シティホールプラザアオーレ長岡
    • Year and Date
      2015-08-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] セリンラセマーゼが触媒するD-セリンデヒドレーション反応の触媒機構2015

    • Author(s)
      松岡舞、伊藤智和、邊見 久、吉村 徹
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] キノコに存在するD-アミノ酸の同定と定量2015

    • Author(s)
      余卓尓、吉野一晴、渡邊彰、伊藤智和、邊見久、麻田恭彦、吉村徹
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山大学
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Properties of GabR, a pyridoxal 5'-phosphate-dependent transcriptional regulator of Bacillus subtilis2014

    • Author(s)
      Tohru Yoshimura, Keita Okuda, Shiro Kato, Hisashi Hemmi, Tomokazu Ito
    • Organizer
      Japan-Italy Joint Symposium: New Trends in Science and Engineering of Enzyme and Microbiology for Sustainable Society
    • Place of Presentation
      奈良市
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Development of enzymatic D-serine assay method and application to urinary D-serine assay2014

    • Author(s)
      Saki Ishizuka, Hiroe takada, Tomokazu Ito, Hisashi Hemmi, Katsumi Shibata, Tohru Yoshimura
    • Organizer
      Japan-Italy Joint Symposium: New Trends in Science and Engineering of Enzyme and Microbiology for Sustainable Society
    • Place of Presentation
      奈良市
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Serine Racemase in Dictyostelium discoideum2014

    • Author(s)
      Saki Kobayashi, Natsuki HAMAUCHI, Tomokazu ITO, Hisashi HEMMI, Yukie SATO, Tamao SAITO, Tohru YOSHIMURA
    • Organizer
      The 2nd International Conference of D-Amino Acid Research
    • Place of Presentation
      宇都宮市
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Conserved Pyridoxal Protein that Regulates Ile and Val Metabolism2014

    • Author(s)
      Tomokazu Ito, Hisashi Hemmi, Tohru Yoshimura
    • Organizer
      Japan-Italy Joint Symposium: New Trends in Science and Engineering of Enzyme and Microbiology for Sustainable Society
    • Place of Presentation
      奈良市
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] E. coliのビタミンB6結合タンパク質YggSの欠損によるオフタルミン酸の蓄積とその要因2014

    • Author(s)
      山内綾子、伊藤智和、邊見久、吉村徹
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都市
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reaction mechanism of eukaryotic serine racemase2014

    • Author(s)
      Tohru Yoshimura, Mai Matsuoka, Hisashi Hemmi, Tomokazu Ito
    • Organizer
      The 2nd International Conference of D-Amino acid Research
    • Place of Presentation
      宇都宮市
    • Year and Date
      2014-09-02 – 2014-09-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] D-SERINE METABOLISM IN CELLULAR SLIME MOLD AND EFFECTS OF D-SERINE DEHYDRATASE MUTATION2014

    • Author(s)
      Tomokazu ITO, Natsuki HAMAUCHI, Hisashi HEMMI, Tamao SAITO, Tohru YOSHIMURA
    • Organizer
      The 2nd International Conference of D-Amino acid Research
    • Place of Presentation
      宇都宮市
    • Year and Date
      2014-09-02 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Catalytic mechanism of PLP- and Zn2+-dependent D-serine dehydratase2014

    • Author(s)
      Tomokazu Ito, Mai Matsuoka, Hisashi Hemmi, Tohru Yoshimura
    • Organizer
      4th International Conference on Cofactors (ICC-04)
    • Place of Presentation
      Parma,Italy
    • Year and Date
      2014-08-25 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ビタミンB 6 酵素の構造,機能進化に関する研究2014

    • Author(s)
      吉村 徹
    • Organizer
      日本ビタミン学会第66回大会
    • Place of Presentation
      姫路市
    • Year and Date
      2014-06-13 – 2014-06-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 亜鉛依存性D-セリンデヒドラターゼの反応機構:PLPピリジン環窒素の相互作用残基(Y203)の変異体解析2014

    • Author(s)
      伊藤智和、松岡舞、邊見久、吉村徹
    • Organizer
      日本ビタミン学会第 66回大会
    • Place of Presentation
      姫路市
    • Year and Date
      2014-06-13 – 2014-06-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] D-アミノ酸:基礎研究から応用へ2014

    • Author(s)
      吉村 徹
    • Organizer
      第2回置賜マイクロ・ナノバイオフォーラム
    • Place of Presentation
      米沢市・置賜文化ホール
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ビタミンB6が担うD-セリンの代謝と機能:セリンラセマーゼとD-セリンデヒドラターゼ2014

    • Author(s)
      吉村 徹
    • Organizer
      ビタミンB研究委員会平成25年度シンポジウム
    • Place of Presentation
      大阪大学中之島センター
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 細胞性粘菌におけるD-セリン代謝酵素欠損の影響2014

    • Author(s)
      伊藤智和、濱内菜月、邊見久、吉村徹
    • Organizer
      2014年度日本農芸化学会大会
    • Place of Presentation
      明治大学生田キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] D-アミノ酸の新機能とその代謝関連酵素の応用2013

    • Author(s)
      吉村 徹
    • Organizer
      酵素工学研究会 第69回講演会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Eucaryotic D-serine dehydratase: reaction mechanism and application to D-serine assay2013

    • Author(s)
      Tohru Yoshimura
    • Organizer
      17thGerman-Japan Workshop on Enzyme Technology
    • Place of Presentation
      Technical University, Hamburg
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] D-アミノ酸オキシダーゼとその応用2013

    • Author(s)
      吉村 徹、邊見久、加藤志郎
    • Organizer
      第65回日本生物工学会大会シンポジウム
    • Place of Presentation
      広島国際会議場
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-21   Modified: 2019-07-29  

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