Generation of ribozymes that catalyze fatty acid biosynthesis

• Project/Area Number: 16101007
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: The University of Tokyo
• Principal Investigator: SUGA Hiroaki The University of Tokyo, 先端科学技術研究センター, 教授 (00361668)
• Co-Investigator(Kenkyū-buntansha): 村上 裕 東京大学, 先端科学技術, 助教 (10361669)
• Co-Investigator(Renkei-kenkyūsha): 二井 一樹 東京大学, 先端科学技術研究センター, 特任研究員 (30418644)
• Research Collaborator: 神 紘 一郎 , 博士大学院生 ; 大内 政樹 , 博士大学院生 ; 太田 淳 , 博士大学院生 ; 川上 隆史 , 博士大学院生 ; 丹羽 慶吉 , 博士大学院生
• Project Period (FY): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥112,060,000 (Direct Cost: ¥86,200,000、Indirect Cost: ¥25,860,000); Fiscal Year 2008: ¥21,580,000 (Direct Cost: ¥16,600,000、Indirect Cost: ¥4,980,000); Fiscal Year 2007: ¥21,580,000 (Direct Cost: ¥16,600,000、Indirect Cost: ¥4,980,000); Fiscal Year 2006: ¥21,580,000 (Direct Cost: ¥16,600,000、Indirect Cost: ¥4,980,000); Fiscal Year 2005: ¥21,580,000 (Direct Cost: ¥16,600,000、Indirect Cost: ¥4,980,000); Fiscal Year 2004: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
• Keywords: リボザイム / RNA 触媒 / 分子進化 / 特殊ペプチド / RNA触媒 / RNA / RNAワールド / バイオテクノロジー / 試験管内進化 / 翻訳 / 生命の起源 / 脂質膜 / 分子進化工学 / 生命体 / アセチルCoA / 酸化還元酵素

Research Abstract

本研究は、 有機化学的なアプローチを試験管内RNA 分子進化法により積極的に取り入れることで複雑且つ洗練された人工リボザイムを創成することに挑んだ。具体的には、脂肪酸生合成に関わる酸化還元リボザイムとtRNA アシル化リボザイムの創製を試み、その応用としてそれらのリボザイムを用いて遺伝暗号リプログラミング技術を開発した。

Research Products

• [Journal Article] Ribosomal synthesis of dehydrobutyrineand methyllanthionine-containing peptides (2009)
  • Author(s): Y. Goto, K. Iwasaki, K. Torikai, H. Murakami, H. Suga
  • Journal Title: Chemical Communication (in press)
• [Journal Article] A flexizyme that selectively charges amino acids activated with awater-friendly leaving group (2009)
  • Author(s): N. Niwa, Y. Yamagishi, H. Murakami, H. Suga
  • Journal Title: Bioorganic Medicinal Chemistry Letter (in press)
• [Journal Article] Translation initiation with initiator tRNA charged with exotic peptides (2009)
  • Author(s): Y. Goto, H. Suga
  • Journal Title: Journal of American Chemical Society 131 Pages: 5040-5041
• [Journal Article] Bases in the anticodons loop of tRNA^<Ala> GGC prevent misreading (2009)
  • Author(s): H. Murakami, A. Ohta, H. Suga
  • Journal Title: Nature Structural & Molecular Biology 16 Pages: 353-358
• [Journal Article] Ribosomal synthesis of dehydrobutyrine-and methyllanthinonine-containing (2009)
  • Author(s): Y. Goto, H. Suga
  • Journal Title: Chemical Communication (in press掲載確定)
  • Peer Reviewed
• [Journal Article] Ribosomal Synthesis of Peptides with C-Terminal Lactams, Thiolactones, and Alkylamides (2009)
  • Author(s): E. Nakajima, Y. Goto, Y. Sako, H. Murakami and H. Suga
  • Journal Title: ChemBioChem (in press掲載確定)
  • Peer Reviewed
• [Journal Article] A flexizyme that selectively charges ameno activated with a water-friendly leaving group (2009)
  • Author(s): N. Niwa, Y. Yamagishi, H. Murakami, H. Suga
  • Journal Title: Bioorganic Medicinal Chemistry Letter (in press掲載確定)
  • Peer Reviewed
• [Journal Article] Bases in the anticodons loop of tRNAAlaGGC prevent misreading (2009)
  • Author(s): H. Murakami, A.Ohta, H.Suga
  • Journal Title: Nature Structural &Molecular Biology 16 Pages: 353-358
  • Peer Reviewed
• [Journal Article] Ribosomal synthesis of polypeptoids and peptoid-peptide hybrids (2008)
  • Author(s): T.Kawakami, H. Murakami, H. Suga
  • Journal Title: Journal of American Chemical Society 130 Pages: 16861-16863
• [Journal Article] Expression of histone H3 tailswith combinatorial lysinemodifications under thereprogrammed genetic code for theinvestigation on epigenetic markers (2008)
  • Author(s): T.-J. Kang, S. Yuzawa, H. Suga
  • Journal Title: Chemistry &Biology 15 Pages: 1166-1174
• [Journal Article] Polymerization of α-hydroxy acids by ribosomes (2008)
  • Author(s): A. Ohta, H. Murakami, H. Suga
  • Journal Title: ChemBioChem (in press)
• [Journal Article] Strcutural basis of specific tRNAaminoacylation by a small in vitroselected ribozyme (2008)
  • Author(s): H. Xiao, H. Murakami, H. Suga
  • Journal Title: A. R. Ferre-D'Amare Nature 454 Pages: 358-361
• [Journal Article] Ribosomal synthesis of bicyclicpeptides with two orthogonalinter-sidechain reactions (2008)
  • Author(s): Y. Sako, J. Morimoto, H. Murakami, H. Suga
  • Journal Title: Journal of American Chemical Society 130 Pages: 7932-7934
• [Journal Article] Initiating translation with D-amino acids (2008)
  • Author(s): Y. Goto, H. Murakami, H. Suga
  • Journal Title: RNA 14 Pages: 1399-1410
• [Journal Article] Ribosomal synthesis of nonstandard peptides (2008)
  • Author(s): T.-J. Kang, H. Suga
  • Journal Title: Biochemistry and Cell Biology 86 Pages: 92-99
• [Journal Article] Synthesis of biopolymers using genetic code reprogramming (2008)
  • Author(s): A. Ohta, Y. Yamagishi, H. Suga
  • Journal Title: Current Opinion in Chemical Biology 12 Pages: 159-167
• [Journal Article] Ribosomal synthesis of peptidase-resistant peptides closed by a non-reducible inter-sidechain bond (2008)
  • Author(s): Y. Sako, Y. Goto, H. Murakami, H. Suga
  • Journal Title: ACS Chemical Biology 3 Pages: 241-249
• [Journal Article] Reprogramming the initiation event in translation for the synthesis of physiologically stable cyclic peptides (2008)
  • Author(s): Y.Goto, A. Ohta, Y. Sako, Y. Yamagishi, H.Murakami, H. Suga
  • Journal Title: ACS Chemical Biology 3 Pages: 120-129
• [Journal Article] Messenger RNA-directed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides (2008)
  • Author(s): T. Kawakami, H. Murakami, H. Suga
  • Journal Title: Chemistry &Biology 15 Pages: 32-42
• [Journal Article] Ribosomal synthesisi of polypeptoids and peptoid-peptide hybrids (2008)
  • Author(s): T.Kawakami, H.Murakami, H.Suga
  • Journal Title: Journal of American Chemical Society 130 Pages: 16861-16863
  • Peer Reviewed
• [Journal Article] Expression of histone H3 tails with combinatorial lysine modifications under the reprogrammed genetic code for the investigation on epigenetic markers (2008)
  • Author(s): T. J. Kang, S. Yuzawa, H. Suga
  • Journal Title: Chemistry & Bioloty 15 Pages: 1166-1174
  • Peer Reviewed
• [Journal Article] Polymerization of a-hydroxy acids by ribosomes (2008)
  • Author(s): A. Ohta, H. Murakami, H. Suga
  • Journal Title: ChemBioChem 9 Pages: 2773-2778
  • Peer Reviewed
• [Journal Article] Strcutural basis of specific tRNA aminoacylattion by a small in vitro selected ribozyme (2008)
  • Author(s): H. Xiao, H. Murakami, H. Suga, A. R. Ferre-D'Amare
  • Journal Title: Nature 454 Pages: 358-361
  • Peer Reviewed
• [Journal Article] Ribosomal synthesis of bicyclic peptides with two orthogomal inter-sidechain (2008)
  • Author(s): Y. Sako, J Morimoto, H. Murakami, H. Suga
  • Journal Title: Journal of American Chemical Society 130 Pages: 7932-7934
  • Peer Reviewed
• [Journal Article] Ribosomal synthesis of nonstandard peptides (2008)
  • Author(s): T. J. Kang, H. Suga
  • Journal Title: Biochemistry and Cell Biology 86 Pages: 92-99
  • Peer Reviewed
• [Journal Article] Symthesis of biopolymers using genetic code reprogramming (2008)
  • Author(s): A. Ohta, Y. Yamagishi, H. Suga
  • Journal Title: Current Opinion in Chemical Biology 12 Pages: 159-167
  • Peer Reviewed
• [Journal Article] Reprogramming the initiation ebent in translation for the synthesisi of physiologically stable cyclic peptides (2008)
  • Author(s): Y. Goto, A. Ohta, Y. Sako, Y. Yamagishi, H.Murakami, H.
  • Journal Title: ACS Chemical Biology 3 Pages: 120-129
  • Peer Reviewed
• [Journal Article] Messenger RNA-directed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides (2008)
  • Author(s): T. Kawakami, H. Murakami, H. Suga
  • Journal Title: Chemistry & Biology 15 Pages: 32-42
  • Peer Reviewed
• [Journal Article] Ribosomal synthesis of peptidase-resistant peptides closed by a non-reducible inter-sidechain bond (2008)
  • Author(s): Y. Sako, Y. Goto, H. Murakami, H. Suga
  • Journal Title: ACS Chemical Biology 44(in press)
  • Peer Reviewed
• [Journal Article] Reprogramming the initiation event in translation for the synthesis of physiologically stablecyclic peptides (2008)
  • Author(s): Y. Goto, A. Ohta, Y. Sako, Y. Yamagishi, H. Murakami, H. Suga
  • Journal Title: ACS Chemical Biology 4 Pages: 120-129
  • Peer Reviewed
• [Journal Article] Messeriger RNA-directed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides (2008)
  • Author(s): T. Kawakami, H. Murakami, H. Suga
  • Journal Title: Chemistty and Biology 14 Pages: 32-42
  • Peer Reviewed
• [Journal Article] Exploration of incorporation of Nalpha-methylated amino acids into peptides by sense-suppression method (2008)
  • Author(s): T. Kawakami, H. Murakami, H. Suga
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 361-362
  • Peer Reviewed
• [Journal Article] Synthesis of polyester by means of genetic code reprogramming (2007)
  • Author(s): A. Ohta, H. Murakami, E. Higashimura, H. Suga
  • Journal Title: Chemistry and Biology 13 Pages: 1315-1322
  • Peer Reviewed
• [Journal Article] The flexizyme system:A highly flexible tRNA aminoacyation tool for thr translation apparatus (2007)
  • Author(s): M. Ohuchi, H. Murakami, H. Suga
  • Journal Title: Current Opinion in Chemistry and Biology 11 Pages: 134-144
  • Peer Reviewed
• [Journal Article] Re-engineering an in-vitro evolved ribozyme (2007)
  • Author(s): S. Pattnaik, H. Suga
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 381-382
  • Peer Reviewed
• [Journal Article] In vitro selection of a 5'-purinenucleotide transferase ribozyme (2007)
  • Author(s): T.-J. Kang, H. Suga
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 379-380
  • Peer Reviewed
• [Journal Article] Exploration of ineorporation of Nalpha-methylated amino acids into peptides by sense-suppression method (2007)
  • Author(s): T. Kawakami, H. Murakami, H. Suga
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 361-362
  • Peer Reviewed
• [Journal Article] In situ generation of aminoacyl-tRNAs assisted by ribozymes in translation apparatus (2007)
  • Author(s): M. Ohuchi, H. Murakami, H. Suga
  • Journal Title: Nucleic Acids Symposium Series 51 Pages: 361-362
  • Peer Reviewed
• [Journal Article] 遺伝暗号のリプログラミング (2007)
  • Author(s): 佐古 佑介・村上 裕・菅裕 明
  • Journal Title: 蛋白質核酸酵素 52 Pages: 1643-1648
• [Journal Article] In vitro selection of a 5'-purine ribonucleotide transferase ribozyme (2007)
  • Author(s): Taek-Jin Kang, Hiroaki Suga
  • Journal Title: Nucleic Acid Research (In press)
• [Journal Article] 遺伝暗号リプログラミングによるポリエステルの翻訳合成 (2007)
  • Author(s): 太田 淳, 村上 裕, 菅 裕明
  • Journal Title: 高分子 56・4月号 Pages: 196-199
• [Journal Article] 特殊ペプチドのコンビナトリアル翻訳合成 (2007)
  • Author(s): 後藤佑樹, 太田淳, 村上裕, 菅裕明
  • Journal Title: 化学工業 58・4月号 Pages: 255-262
• [Journal Article] A highly flexible tRNA acylation system for nonnatural polypeptide synthesis (2006)
  • Author(s): Hiroshi Murakami, Atsushi Ohta, Hiroshi Ashigai, Hiroaki Suga
  • Journal Title: Nature Methods 3 Pages: 357-359
• [Journal Article] In vitro evolution of flexizymes that function under the conditions in translation system (2006)
  • Author(s): Masaki Ohuchi, Hiroshi Murakami, Hiroaki Suga
  • Journal Title: Nucleic Acids Symposium Series 50 Pages: 299-300
• [Journal Article] Ribosomal synthesis of peptides having various acyl groups on the N-terminus (2006)
  • Author(s): Yuki Goto, Hiroshi Ashigai, Yusuke Sako, Hiroshi Murakami, Hiroaki Suga
  • Journal Title: Peptide Science 43 Pages: 46-47
  • NAID: 10020528886
• [Journal Article] Ribosomal synthesis of non-natural peptide using the flexizyme system (2006)
  • Author(s): Hiroshi Murakami, Atsushi Ohta, Yuki Goto, Yusuke Sako, Hiroaki Suga
  • Journal Title: Peptide Science 43 Pages: 48-49
  • NAID: 10020528891
• [Journal Article] Translation initiation by using various N-acylaminoacyl tRNAs (2006)
  • Author(s): Yuki Goto, Hiroshi Ashigai, Yusuke Sako, Hiroshi Murakami, Hiroaki Suga
  • Journal Title: Nucleic Acids Symposium Series 50 Pages: 293-294
• [Journal Article] A novel therapeutic approach for genetic diseases by introduction of suppressor tRNA (2006)
  • Author(s): Yusuke Sako, Fusako Usuki, Hiroaki Suga
  • Journal Title: Nucleic Acids Symposium Series 50 Pages: 239-240
• [Journal Article] Flexizyme as a versatile tRNA acylation catalyst and the application for translation (2006)
  • Author(s): Hiroshi Murakami, Atsushi Ohta, Yuki Goto, Yusuke Sako, Hiroaki Suga
  • Journal Title: Nucleic Acids Symposium Series 50 Pages: 35-36
• [Journal Article] フレキシザイム-遺伝暗号の拡張とリプログラミングへの応用 (2006)
  • Author(s): 村上 裕, 菅 裕明
  • Journal Title: バイオテクノロジージャーナル 6・11/12月号 Pages: 2496-2501
• [Journal Article] フレキシザイムを用いた遺伝暗号の拡張とリプログラミング (2006)
  • Author(s): 村上 裕, 菅 裕明
  • Journal Title: 蛋白質核酸酵素 51・16 Pages: 28-33
• [Journal Article] A highly flexible tRNA acylation system for nonnatural polypeptide synthesis (2006)
  • Author(s): Hiroshi Murakami, Atsushi Ohta, Hiroshi Ashigai, Hiroaki Suga
  • Journal Title: Nature Methods in press
• [Journal Article] 合成生物学・その概念と未来 (2006)
  • Author(s): 木賀大輔, 菅 裕明
  • Journal Title: バイオニクス・オーム社 3月号 Pages: 28-33
• [Journal Article] セントラルドグマをつくりかえる (2006)
  • Author(s): 村上 裕, 菅 裕明, 平尾一郎
  • Journal Title: バイオニクス・オーム社 3月号 Pages: 34-39
• [Journal Article] 細胞内情報をあやつる (2006)
  • Author(s): 築地真也, 菅 裕明, 長棟輝行
  • Journal Title: バイオニクス・オーム社 3月号 Pages: 46-51
• [Journal Article] Programmable ribozymes for misoharging tRNA with nonnatural amino acids and their applications to translation (2005)
  • Author(s): Dimitrios Kourouklis, Hiroshi Murakami, Hiroaki Suga
  • Journal Title: Methods 36(3) Pages: 239-244
• [Journal Article] 人工リボザイムでRNAワールドの検証に挑む (2005)
  • Author(s): 菅 裕明
  • Journal Title: 現代化学 6月号 Pages: 44-50
  • NAID: 40006766368
• [Journal Article] Reduction of an aldehyde by a NADH/Zn^<2+>-dependent redox active ribozyme (2004)
  • Author(s): S.Tsukiji, S.Pattnaik, H.Suga
  • Journal Title: Journal of American Chemical Society 126 Pages: 5044-5045
• [Journal Article] Ribozymes that use redox cofactors (2004)
  • Author(s): S.Tsukiji, K.Ramaswamy, H.Suga
  • Journal Title: Journal Pure and Applied Chemistry 76 Pages: 1525-1536
• [Presentation] 第2次先端ウオッチング-生合成化学 (2009)
  • Author(s): 菅
  • Organizer: 日本化学会年会
  • Place of Presentation: 西船橋
  • Year and Date: 2009-03-27
• [Presentation] 特殊ペプチドの翻訳合成:創薬への展開 (2009)
  • Author(s): 菅裕明
  • Organizer: 日本化学会
  • Place of Presentation: 西船橋・日大キャンパス
  • Year and Date: 2009-03-27
• [Presentation] ETH Zurich (2009)
  • Author(s): 菅
  • Organizer: Institute of Organic Chemistry Seminar
  • Place of Presentation: Zurich, Switzerland
  • Year and Date: 2009-01-08
• [Presentation] RIKEN Conference (2008)
  • Author(s): 菅
  • Organizer: Chemical Biology
  • Place of Presentation: 成田
  • Year and Date: 2008-11-12
• [Presentation] Chemical Biology of non-standard peptides (2008)
  • Author(s): 菅裕明
  • Organizer: RIKEN Conference in Chemical Biology
  • Place of Presentation: 成田
  • Year and Date: 2008-11-12
• [Presentation] Japanese-German Frontier of Science (2008)
  • Author(s): 菅
  • Organizer: Heidelberg
  • Place of Presentation: Germany
  • Year and Date: 2008-10-30
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: BioJapan
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-16
• [Presentation] International Symposium on Molecular Recognition of DNA (2008)
  • Author(s): 菅
  • Organizer: Biological Applications
  • Place of Presentation: 東京
  • Year and Date: 2008-09-16
• [Presentation] Veyrier du Lac (2008)
  • Author(s): 菅
  • Organizer: Aminoacyl-tRNA Synthetase Meeting 2008
  • Place of Presentation: France
  • Year and Date: 2008-09-11
• [Presentation] of Methods in Protein Structural Analysis (2008)
  • Author(s): 菅
  • Organizer: The 17th Meeting
  • Place of Presentation: 札幌
  • Year and Date: 2008-08-28
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: 前期有機合成化学講習会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-18
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: 第56回日本化学療法学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2008-06-17
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: 第7回新規素材探索研究会セミナー
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-06
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: 日本ケミカルバイオロジー研究会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-05-19
• [Presentation] 特殊ペプチドの翻訳合成:創薬への展開 (2008)
  • Author(s): 菅裕明
  • Organizer: 日本ケミカルバイオロジー研究会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-05-19
• [Presentation] (2008)
  • Author(s): 菅
  • Organizer: 第128回日本薬学会年会・特別講演
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Book] セルアラカルト : ケミカルバイオロジーの夜明けから20年、潮流が大きな波に変わるには (2009)
  • Author(s): 菅裕明
  • Publisher: 細胞工学
• [Book] 鳥飼浩平 (2009)
  • Author(s): 鳥飼浩平・菅裕明
  • Publisher: ファルマシア
• [Book] 「特殊ペプチドの翻訳合成と薬剤探索」新規素材探索-医薬品リード化合物・食品素材を求めて- (2008)
  • Author(s): 菅裕明・山岸祐介
  • Publisher: シーエムシー出版
• [Book] 新創薬技術RAPIDシステムとマイクロ・ナノディバイスへの期待 (2008)
  • Author(s): 村上裕・菅裕明
  • Publisher: 化学工業
• [Remarks]
  • URL: http://www.cbl.rcast-tokyo.ac.jp
• [Patent(Industrial Property Rights)] 環状化学物ペプチドの合成法 (2007)
  • Inventor(s): 菅 裕明, 村上 裕, 後藤佑樹, 山岸祐介, 足海洋史, 佐古佑介
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2007-080141
  • Filing Date: 2007-03-26
• [Patent(Industrial Property Rights)] N末端に非天然骨格を持つポリペプチドの翻訳合成とその応用 (2006)
  • Inventor(s): 菅 裕明, 村上 裕, 後藤佑樹, 太田 淳
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2006-312000
  • Filing Date: 2006-11-17