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Development of artificial natural products

Research Project

Project/Area Number 15K12739
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Goto Yuki  東京大学, 大学院理学系研究科(理学部), 准教授 (70570604)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsペプチド / 主鎖修飾ペプチド / 人工生合成系 / 翻訳後修飾 / 化学修飾
Outline of Final Research Achievements

Peptidic natural products often consist of not only simple amide bonds but also modified backbones. Since such unique backbones are important structural motifs that contribute to diverse bioactivities, peptides with modified backbones can also be attractive candidates for artificial bioactive peptides. This research program devised an in vitro biosynthesis system referred to as FIT-PatD system by the integration of an engineered cell-free translation system with a posttranslational cyclodehydratase, enabling “one-pot” synthesis of a wide variety of azoline-containing peptide derivatives expressed from synthetic DNA templates. Moreover, we have demonstrated in vitro biosynthesis of peptides with various backbone structures by combination of the FIT-PatD system and chemical modifications. These results offer the potentials for the production of a wide collection of backbone-modified peptides and may facilitate the discovery of “peudo-natural” bioactive peptides.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (28 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 13 results)

  • [Journal Article] Elaboration of Pseudo-natural Products Using Artificial <i>In Vitro</i> Biosynthesis Systems2018

    • Author(s)
      後藤佑樹
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 138 Issue: 1 Pages: 55-61

    • DOI

      10.1248/yakushi.17-00186-3

    • NAID

      130006300866

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2018-01-01
    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Quality control by trans-editing factor prevents global mistranslation of non-protein amino acid α-aminobutyrate.2018

    • Author(s)
      Bacusmo JM, Kuzmishin AB, Cantara WA, Goto Y, Suga H, Musier-Forsyth K.
    • Journal Title

      RNA Biol.

      Volume: 15 Issue: 4-5 Pages: 576-585

    • DOI

      10.1080/15476286.2017.1353846

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Artificial Division of Codon Boxes for Expansion of the Amino Acid Repertoire of Ribosomal Polypeptide Synthesis.2018

    • Author(s)
      Iwane Y, Katoh T, Goto Y, Suga H.
    • Journal Title

      Methods Mol Biol.

      Volume: 1728 Pages: 17-47

    • DOI

      10.1007/978-1-4939-7574-7_2

    • ISBN
      9781493975730, 9781493975747
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly selective inhibition of histone demethylases by de novo macrocyclic peptides.2017

    • Author(s)
      Kawamura A, Mnzel M, Kojima T, Yapp C, Bhushan B, Goto Y, Tumber A, Katoh T, King ON, Passioura T, Walport LJ, Hatch SB, Madden S, Muller S, Brennan PE, Chowdhury R, Hopkinson RJ, Suga H, Schofield CJ.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 14773-14773

    • DOI

      10.1038/ncomms14773

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conformational and chemical selection by a trans-acting editing domain.2017

    • Author(s)
      Danhart EM, Bakhtina M, Cantara WA, Kuzmishin AB, Ma X, Sanford BL, Vargas-Rodriguez O, Ko; M, Goto Y, Suga H, Nakanishi K, Micura R, Foster MP, Musier-Forsyth K.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114 Issue: 33

    • DOI

      10.1073/pnas.1703925114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficient siRNA Delivery by Lipid Nanoparticles Modified with a Nonstandard Macrocyclic Peptide for EpCAM-Targeting.2017

    • Author(s)
      Sakurai Y, Mizumura W, Murata M, Hada T, Yamamoto S, Ito K, Iwasaki K, Katoh T, Goto Y, Takagi A, Kohara M, Suga H, Harashima H.
    • Journal Title

      Mol Pharm

      Volume: 14 Issue: 10 Pages: 3290-3298

    • DOI

      10.1021/acs.molpharmaceut.7b00362

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ribosomal synthesis of peptides with multiple beta-amino acids2016

    • Author(s)
      Fujino, T. Goto, Y. Suga, H. Murakami, H.
    • Journal Title

      J Am Chem Soc

      Volume: 138 Issue: 6 Pages: 1962-1969

    • DOI

      10.1021/jacs.5b12482

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A fluorescent imaging probe based on a macrocyclic scaffold that binds to cellular EpCAM2015

    • Author(s)
      Iwasaki, K. Goto, Y. Katoh, T. Yamashita, T. Kaneko, S. Suga, H.
    • Journal Title

      J Mol Evol

      Volume: 81 Issue: 5-6 Pages: 210-217

    • DOI

      10.1007/s00239-015-9710-z

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Homologous trans-editing factors with broad tRNA specificity prevent mistranslation caused by serine/threonine misactivation2015

    • Author(s)
      Liu, Z. Vargas-Rodriguez, O. Goto, Y. Novoa, E. M. Ribas de Pouplana, L. Suga, H. Musier-Forsyth, K.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 112 Issue: 19 Pages: 6027-6032

    • DOI

      10.1073/pnas.1423664112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Laser-induced oxidation of a peptide-embedded thiazoline by an assistance of adjacent thiazoline2015

    • Author(s)
      Kato, Y. Goto, Y. Suga, H.
    • Journal Title

      Peptide Science

      Volume: 52 Pages: 27-28

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 特殊ペプチドがもつ中分子創薬に向けたポテンシャル2017

    • Author(s)
      後藤 佑樹、菅 裕明
    • Organizer
      構造活性フォーラム2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Ribosomal synthesis of bicyclic peptides using artificial amino acids with tunable reactivities2017

    • Author(s)
      Y. Goto、N. Ozawa、 H. Suga
    • Organizer
      american peptide symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 人工生合成系を活用した擬天然物の創製戦略2017

    • Author(s)
      後藤 佑樹
    • Organizer
      環境微生物系学会合同大会2017微生物を使った「ものづくり」最前線~代謝物から酵素まで~
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Development of bioactive pseudo-natural peptides using artificial in vitro biosynthesis systems2017

    • Author(s)
      Yuki Goto
    • Organizer
      1st China-Japan Joint Symposium on Natural Product Biosynthesis
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 擬天然物の創製を指向した試験管内人工生合成系2017

    • Author(s)
      後藤 佑樹
    • Organizer
      北陸先端科学技術大学院大学 第11回マテリアルサイエンス系セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 人工生合成系を活用して擬天然物を創製する2017

    • Author(s)
      後藤佑樹
    • Organizer
      Conbio2017 疾患関連分子の認識技術の革新
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物を創る2017

    • Author(s)
      後藤 佑樹
    • Organizer
      Waters ペプチド医薬品分析セミナー@東京
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物を創る2017

    • Author(s)
      後藤 佑樹
    • Organizer
      Waters ペプチド医薬品分析セミナー@大阪
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 調節可能な共有結合性阻害能を示す環状ペプチドの創製2017

    • Author(s)
      小澤 直也・後藤 佑樹・菅 裕明
    • Organizer
      日本化学会第98春季年会 ケミカルバイオロジー研究加速のための生物活性分子の発見戦略
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系を活用した擬天然物の創製2016

    • Author(s)
      後藤佑樹
    • Organizer
      日本薬学会第136年会 「メタボライトとエピゲノム」シンポジウム
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] In vitro biosynthesis of backbone-modified peptides by post-translational modification reactions2016

    • Author(s)
      Yasuharu Kato, Yuki Goto, Hiroaki Suga
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学 京田辺校地(京都府・京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 擬天然物の創成を見据えた人工生合成系の確立2016

    • Author(s)
      後藤佑樹
    • Organizer
      人工タンパク質の合成生物学ワークショップ
    • Place of Presentation
      理化学研究所 横浜キャンパス(神奈川県・横浜市)
    • Year and Date
      2016-01-06
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] In vitro biosynthetic system for peptides with diverse heterocycles towards development of pseudo-natural products2015

    • Author(s)
      Yuki Goto
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] In vitro biosynthetic system for peptides with diverse peptide-mimetic backbones2015

    • Author(s)
      Yuki Goto, Yasuharu Kato, Hiroaki Suga
    • Organizer
      7th International Peptide Symposium
    • Place of Presentation
      Singapore
    • Year and Date
      2015-12-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Incorporation of artificial amino acids by reconstitution of in vitro translation apparatus2015

    • Author(s)
      Yuki Goto, Hiroaki Suga
    • Organizer
      Biochemistry and Molecular Biology 2015
    • Place of Presentation
      神戸国際会議場 (兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Oxidation of azolines assisted by an adjacent azoline moiety toward in vitro synthesis of azole-containing peptides2015

    • Author(s)
      Yasuharu Kato, Yuki Goto, Hiroaki Suga
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      平塚中央公民館(神奈川県・平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Presentation] In vitro biosynthetic system for peptides with diverse backbone heterocycles2015

    • Author(s)
      Yuki Goto, Yasuharu Kato, Hiroaki Suga
    • Organizer
      16th International Symposium on Advancing the Chemical Science
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2015-06-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 改変翻訳反応を用いた特殊環状ペプチドの合成~何を考えながら研究に取り組むべきか~2015

    • Author(s)
      後藤佑樹、菅裕明
    • Organizer
      GEヘルスケア Life Sciences Academyはじめてのライフサイエンス基礎講座 2015
    • Place of Presentation
      蚕糸科学研究所(東京都・新宿区)
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2020-03-17  

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