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Ribosome modification to synthesize peptides containing beta-amino acids

Research Project

Project/Area Number 18K14332
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionNagoya University

Principal Investigator

Fujino Tomoshige  名古屋大学, 工学研究科, 助教 (00772378)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsリボソーム / 無細胞翻訳系 / β-アミノ酸 / D体アミノ酸 / ペプチド / 進化分子工学 / 翻訳系
Outline of Final Research Achievements

The aim of this study was modifying ribosome, which is the organelle producing proteins in a cell, to improve the incorporation efficiency of non-proteinogenic amino acids into peptide. We successfully developed a method to pick up the desired mutant ribosome from the pool of highly diverse mutant ribosomes containing random mutations in their rRNA sequences. Although we found the rRNA sequence with an improved activity to introduce D-amino acid into peptide, the expression and purification of the mutant ribosome from E. coli cells were difficult because the structural stability of the mutant ribosome was low.

Academic Significance and Societal Importance of the Research Achievements

本研究では、目的の機能を持ったリボソームを、進化分子工学によって取得する手法を開発した。この手法は、本研究で対象としたβ-アミノ酸・D体アミノ酸に限定されず、さまざまな特殊アミノ酸を翻訳可能なリボソームの開発に利用できる。今後、特殊アミノ酸の翻訳が自由に行えるようになれば、現在注目されている進化分子工学を利用したペプチド薬剤の開発など、実用的な分野への応用も可能になると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (11 results)

  • [Journal Article] cDNA TRAP display for rapid and stable in vitro selection of antibody-like proteins2021

    • Author(s)
      Kondo Taishi、Eguchi Minori、Kito Seita、Fujino Tomoshige、Hayashi Gosuke、Murakami Hiroshi
    • Journal Title

      Chemical Communications

      Volume: 57 Issue: 19 Pages: 2416-2419

    • DOI

      10.1039/d0cc07541h

    • NAID

      120007169556

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Amino Acid-Swapped Genetic Code2020

    • Author(s)
      Fujino Tomoshige、Tozaki Masahiro、Murakami Hiroshi
    • Journal Title

      ACS Synthetic Biology

      Volume: 9 Issue: 10 Pages: 2703-2713

    • DOI

      10.1021/acssynbio.0c00196

    • NAID

      120006959574

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibody-like proteins that capture and neutralize SARS-CoV-22020

    • Author(s)
      Kondo T.、Iwatani Y.、Matsuoka K.、Fujino T.、Umemoto S.、Yokomaku Y.、Ishizaki K.、Kito S.、Sezaki T.、Hayashi G.、Murakami H.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 42 Pages: 3916-3916

    • DOI

      10.1126/sciadv.abd3916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring the Minimal RNA Substrate of Flexizymes2019

    • Author(s)
      Fujino Tomoshige、Kondo Taishi、Suga Hiroaki、Murakami Hiroshi
    • Journal Title

      ChemBioChem

      Volume: 20 Issue: 15 Pages: 1959-1965

    • DOI

      10.1002/cbic.201900150

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 若手研究者からのメッセージ2018

    • Author(s)
      藤野公茂
    • Journal Title

      日本化学会バイオテクノロジー部会ニュースレター

      Volume: 22 Pages: 12-16

    • Related Report
      2018 Research-status Report
  • [Presentation] High-speed selection of antibody-like proteins that capture and neutralize SARS-CoV-22021

    • Author(s)
      近藤太志、岩谷靖雅、松岡和弘、藤野公茂、梅本駿、横幕能行、林剛介、村上裕
    • Organizer
      The 18th Akabori Conference
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高速人工抗体創製法の開発とSARS-CoV-2中和抗体作製への応用2020

    • Author(s)
      近藤太志、岩谷靖雅、松岡和弘、藤野公茂、梅本駿、横幕能行、林剛介、村上裕
    • Organizer
      生物化学的測定研究会 第25回学術シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] SARS-CoV-2を結合・中和する人工抗体の開発2020

    • Author(s)
      近藤太志、岩谷靖雅、松岡和弘、藤野公茂、梅本駿、横幕能行、林剛介、村上裕
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] アミノ酸入れ替え遺伝暗号の開発2020

    • Author(s)
      藤野公茂、戸崎将弘、村上裕
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] SARS-CoV-2由来スパイクタンパク質に対する高親和性人工抗体の高速創製2020

    • Author(s)
      近藤太志、岩谷靖雅、松岡和弘、藤野公茂、梅本駿、横幕能行、林剛介、村上裕
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] フレキシザイムの最小RNA基質の探索2019

    • Author(s)
      藤野公茂,近藤太志,菅裕明,村上裕
    • Organizer
      第13回バイオ関連化学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] フレキシザイムの基質となる最小RNAの探索2019

    • Author(s)
      藤野 公茂,近藤 太志,菅 裕明,村上 裕
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 改変翻訳系の構築を指向した変異リボソームの迅速精製法2018

    • Author(s)
      藤野公茂,秋山尚輝,則武卓磨,村上 裕
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 迅速かつ簡便な変異リボソーム精製法2018

    • Author(s)
      秋山尚輝,則武卓磨,藤野公茂,村上 裕
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] β-アミノ酸を基質とする改変リボソーム選択系の開発2018

    • Author(s)
      則武 卓磨,藤野 公茂,村上 裕
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] β-アミノ酸を基質とする改変リボソーム選択法の確立2018

    • Author(s)
      藤野公茂,則武卓磨,村上裕
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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