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Ribosomal synthesis of polyketide-peptide hybrid molecules

Research Project

Project/Area Number 17H04762
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
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) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2019: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2017: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords翻訳合成 / ポリケチド / ペプチド / 擬天然物 / 生合成
Outline of Final Research Achievements

Many polyketide-peptide hybrid molecules have been isolated as bioactive natural products. In this research, we aimed to establish a new method for ribosomal synthesis of peptides bearing unique polyketide-like moieties. To this end, we tested several different synthetic approaches, and eventually demonstrated that peptides with polyketide-like long backbone structures can be expressed by a combination of in vitro translation and posttranslational acyl transfer reaction. This synthetic method has indeed allowed for in vitro ribosomal synthesis of a model bioactive molecule.

Academic Significance and Societal Importance of the Research Achievements

試験管内翻訳合成法は、中分子薬剤候補の化合物ライブラリー構築と探索に近年活発に活用されている。本研究により試験管内翻訳合成で合成できる化合物のバリエーションを拡大させ、実際に生物活性分子を生産できることが実証されたことは、天然物様のポリケチド-ペプチド複合分子を活用した擬天然物創薬戦略の基盤となりえる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (59 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (22 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 16 results,  Open Access: 10 results) Presentation (33 results) (of which Int'l Joint Research: 7 results,  Invited: 26 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Univ. of North Carolina at Chapel Hill(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Oxford Univ.(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Chemoenzymatic Posttranslational Modification Reactions for the Synthesis of Ψ[CH 2 NH]‐Containing Peptides2020

    • Author(s)
      Kato Yasuharu、Kuroda Tomohiro、Huang Yichao、Ohta Risa、Goto Yuki、Suga Hiroaki
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Issue: 2 Pages: 684-688

    • DOI

      10.1002/anie.201910894

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploring the Post-translational Enzymology of PaaA by mRNA Display2020

    • Author(s)
      Fleming, S. R., Himes, P. M., Ghodge, S. V., Goto, Y., Suga, H., Bowers, A. A.
    • Journal Title

      J Am Chem Soc

      Volume: 142 Issue: 11 Pages: 5024-5028

    • DOI

      10.1021/jacs.0c01576

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Improved Stability of siRNA-Loaded Lipid Nanoparticles Prepared with a PEG-Monoacyl Fatty Acid Facilitates Ligand-Mediated siRNA Delivery2020

    • Author(s)
      Sakurai, Y., Mizumura, W., Ito, K., Iwasaki, K., Katoh, T., Goto, Y., Suga, H., Harashima, H.
    • Journal Title

      Mol Pharm

      Volume: 17 Issue: 4 Pages: 1397-1404

    • DOI

      10.1021/acs.molpharmaceut.0c00087

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ribosomal Formation of Thioamide Bonds in Polypeptide Synthesis2019

    • Author(s)
      Maini Rumit、Kimura Hiroyuki、Takatsuji Ryo、Katoh Takayuki、Goto Yuki、Suga Hiroaki
    • Journal Title

      Journal of the American Chemical Society

      Volume: 141 Issue: 51 Pages: 20004-20008

    • DOI

      10.1021/jacs.9b11097

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meeting Peptides in Kyoto2019

    • Author(s)
      Futaki, S., Matsuzaki, K., Goto, Y.
    • Journal Title

      Chembiochem

      Volume: 20 Issue: 16 Pages: 2015-2016

    • DOI

      10.1002/cbic.201900456

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Generation of non-standard macrocyclic peptides specifically binding TSC-22 homologous gene-12019

    • Author(s)
      Tran STP, Hipolito CJ, Suzuki H, Xie R, Kim Tuyen HD, Dijke PT, Terasaka N, Goto Y, Suga H, Kato M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 516 Issue: 2 Pages: 445-450

    • DOI

      10.1016/j.bbrc.2019.06.035

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vitro Biosynthesis of Peptides Containing Exotic Azoline Analogues2019

    • Author(s)
      Goto Yuki、Suga Hiroaki
    • Journal Title

      ChemBioChem

      Volume: 21 Issue: 1-2 Pages: 84-87

    • DOI

      10.1002/cbic.201900521

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RiPP生合成経路の改変による天然物ペプチドの人工誘導体の合成2019

    • Author(s)
      後藤佑樹
    • Journal Title

      ペプチド創薬の最前線, シーエムシー出版

      Volume: N/A

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ケミカルバイオロジー2.02019

    • Author(s)
      三好大輔, 山東信介, 清中茂樹, 花岡健二郎, 後藤佑樹
    • Journal Title

      現代化学

      Volume: 581 Pages: 18-23

    • Related Report
      2019 Annual Research Report
  • [Journal Article] RiPP生合成経路の改変による人工ペプチド生産2019

    • Author(s)
      後藤 佑樹、井上 澄香、菅 裕明
    • Journal Title

      Farumashia

      Volume: 55 Issue: 7 Pages: 662-667

    • DOI

      10.14894/faruawpsj.55.7_662

    • NAID

      130007671606

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Ribosomal Synthesis of Backbone-Cyclic Peptides Compatible with In Vitro Display.2019

    • Author(s)
      Takatsuji R, Shinbara K, Katoh T, Goto Y, Passioura T, Yajima R, Komatsu Y, Suga H.
    • Journal Title

      J Am Chem Soc.

      Volume: 141 Issue: 6 Pages: 2279-2287

    • DOI

      10.1021/jacs.8b05327

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides.2019

    • Author(s)
      Fleming SR, Bartges TE, Vinogradov AA, Kirkpatrick CL, Goto Y, Suga H, Hicks LM, Bowers AA.
    • Journal Title

      J Am Chem Soc.

      Volume: 141 Issue: 2 Pages: 758-762

    • DOI

      10.1021/jacs.8b11521

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Engineering of RiPP pathways for the production of artificial peptides bearing various non-proteinogenic structures2018

    • Author(s)
      Goto Yuki、Suga Hiroaki
    • Journal Title

      Current Opinion in Chemical Biology

      Volume: 46 Pages: 82-90

    • DOI

      10.1016/j.cbpa.2018.06.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Artificial <i>In Vitro</i> Biosynthesis Systems for the Development of Pseudo-Natural Products2018

    • Author(s)
      Goto Yuki、Suga Hiroaki
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 91 Issue: 3 Pages: 410-419

    • DOI

      10.1246/bcsj.20170379

    • NAID

      130006507065

    • ISSN
      0009-2673, 1348-0634
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Non-competitive cyclic peptides for targeting enzyme?substrate complexes2018

    • Author(s)
      McAllister T. E.、Yeh T.-L.、Abboud M. I.、Leung I. K. H.、Hookway E. S.、King O. N. F.、Bhushan B.、Williams S. T.、Hopkinson R. J.、M?nzel M.、Loik N. D.、Chowdhury R.、Oppermann U.、Claridge T. D. W.、Goto Y.、Suga H.、Schofield C. J.、Kawamura A.
    • Journal Title

      Chemical Science

      Volume: 9 Issue: 20 Pages: 4569-4578

    • DOI

      10.1039/c8sc00286j

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Studies of Intramolecular O-to-N Acyl Transfer Reaction toward Production of Peptides Containing γ-Peptide Moieties2017

    • Author(s)
      Tomohiro Kuroda, Yuki Goto, and Hiroaki Suga
    • Journal Title

      Pep. Sci.

      Volume: 54

    • Related Report
      2017 Annual Research Report
  • [Presentation] One-pot saturation mutagenesis of substrate peptides of posttranslationally modifying enzymes2019

    • Author(s)
      Yuki Goto, Haruka Takeue, Yamato Komatsu, Alexander A. Vinogradov, Hiroaki Suga
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ペプチド薬剤を作る人工生合成システム2019

    • Author(s)
      後藤佑樹
    • Organizer
      第9回 CSJ化学フェスタ2019 究極の化学がここにある!~自然に学び自然に迫る触媒デザイン~
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物を創る2019

    • Author(s)
      後藤佑樹
    • Organizer
      理研 Chemical Probe 第二回合同合宿セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物ペプチドを創る2019

    • Author(s)
      後藤佑樹
    • Organizer
      第71回日本生物工学会大会 生合成工学における有用生体機能分子の次世代創製技術
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物ペプチドを創る2019

    • Author(s)
      後藤佑樹
    • Organizer
      日本遺伝学会第91回大会 WS7 再構成系におけるゲノムの構築・複製・動態
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Artificial in vitro biosynthesis for elaboration of pseudo-natural peptides2019

    • Author(s)
      Yuki Goto
    • Organizer
      10th RSC-CSJ Joint Symposium _ Chemistry for Complex Biological Systems _
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 化学的骨格変換反応による主鎖修飾ペプチドの翻訳合成2019

    • Author(s)
      後藤 佑樹、黒田 知宏、堤見 遥、加藤 保治、菅 裕明
    • Organizer
      第13回バイオ関連化学シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] プレニル化擬天然ペプチドをつくる2019

    • Author(s)
      後藤佑樹
    • Organizer
      細胞構成研究会2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 試験管内人工生合成系で擬天然物をつくる2019

    • Author(s)
      後藤佑樹
    • Organizer
      第7回慶應有機化学若手シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] One-pot saturation mutagenesis of RiPP precursor peptides2019

    • Author(s)
      Yuki Goto
    • Organizer
      First International RiPPs Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 試験管内人工生合成系で擬天然物をつくる2019

    • Author(s)
      後藤佑樹
    • Organizer
      鹿児島大学理学部先端科学講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 中分子創薬を見据えた擬天然ペプチド開発戦略2019

    • Author(s)
      後藤佑樹
    • Organizer
      技術情報協会セミナー「環状ペプチドの探索法と構造・配座解析」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 生合成系を改造して擬天然物を創る2019

    • Author(s)
      後藤佑樹
    • Organizer
      東京工業大学LiHub 創薬技術革新G ワークショップ「創薬関連研究の最先端」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 翻訳反応を改造して擬天然物をつくる2019

    • Author(s)
      後藤佑樹
    • Organizer
      新潟大学UGCE連携教育研究センター第9回シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of tunable and selective protein modifiers based on macrocyclic peptides2019

    • Author(s)
      Y Goto
    • Organizer
      3rd ETH Zurich-UTokyo Strategic Partnership Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 共有結合を介して標的に結合する高選択性中分子化合物の汎用創製手法の確立2018

    • Author(s)
      後藤佑樹
    • Organizer
      第21回生命化学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] mRNAディスプレイ法によるペプチド修飾酵素基質の網羅的変異導入解析2018

    • Author(s)
      後藤佑樹
    • Organizer
      第91回日本生化学会大会物理、化学の力で生物を理解する」シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] In vitro biosynthesis system for peptides with diverse modified backbones2018

    • Author(s)
      Y Goto
    • Organizer
      Asian Synthetic Biology Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of tunable and selective protein modifiers based on macrocyclic peptides2018

    • Author(s)
      Y Goto
    • Organizer
      4th International Conference on Circular Proteins and Peptides 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] mRNA ディスプレイ法によるペプチド修飾酵素基質の網羅的変異導入解析2018

    • Author(s)
      後藤 佑樹・竹植 悠・小松 大和・菅 裕明
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 試験管内リデザイン生合成系で擬天然物を創る2018

    • Author(s)
      後藤佑樹
    • Organizer
      「細胞を創る」研究会 11.0
    • Related Report
      2018 Annual Research Report
    • Invited
  • [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] 炭素主鎖骨格含有ペプチドを合成する翻訳後アシル転移反応の開発2017

    • Author(s)
      黒田知宏、後藤佑樹、菅裕明
    • Organizer
      第5回バイオ関連化学シンポジウム若手フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 炭素主鎖骨格含有ペプチドを合成する翻訳後アシル転移反応の開発2017

    • Author(s)
      黒田知宏、後藤佑樹、菅裕明
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] In vitro synthesis of peptides containing carbon-backbone via post-translational acyl transfer reaction2017

    • Author(s)
      Tomohiro Kuroda, Yuki Goto, and Hiroaki Suga
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物ライブラリー及び化合物ライブラリーの製造方法2018

    • Inventor(s)
      菅 裕明,後藤 佑樹,尾仲 宏康,ヴィノグラドフ アレクサンダー
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチドライブラリーの製造方法2018

    • Inventor(s)
      菅 裕明,後藤 佑樹,阿部 郁朗,岡田 正弘,井上 澄香
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2023-03-23  

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