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2020 Fiscal Year Annual Research Report

人工生合成マシナリーの合理的再構築による次世代天然物化学

Planned Research

Project AreaCreation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries
Project/Area Number 16H06443
Research InstitutionThe University of Tokyo

Principal Investigator

阿部 郁朗  東京大学, 大学院薬学系研究科(薬学部), 教授 (40305496)

Project Period (FY) 2016-06-30 – 2021-03-31
Keywords生合成リデザイン / 合成生物学 / 生合成工学 / 天然物化学 / 生物分子科学
Outline of Annual Research Achievements

糸状菌由来メロテルペノイド等など、複雑骨格天然物の生合成をとりあげる。メロテルペノイドの生合成は、比較的短工程で複雑な分子骨格を構築する点が特徴的であり、これは多段階の劇的な骨格変換反応を触媒する多機能型酸化酵素等の存在によるところが大きい。本研究では、人為的な機能制御と分子多様性創出の格好の材料ともいえる、これら特異な反応を触媒する修飾酵素について、X線結晶構造解析などにより、酵素反応の立体構造基盤を解明し、さらに立体構造情報に基づき酵素機能を合理的な改変をめざした。
酵素の結晶構造解析と構造機能相関の解明。昨年に引き続き、アンジトミン、ノボフミガトニン、アスコフラノン、アスコクロリン、オーシノールなどの生合成において、多段階の劇的な骨格変換反応を触媒し、その構造複雑化に決定的な役割を演じる、多機能型非ヘム鉄要求性ジオキシゲナーゼについて、X線結晶構造解析を行い、酵素反応の立体構造基盤を解明、さらに、結晶構造に基づき、合理的な酵素機能の改変と生合成リデザインに成功した。結果を印刷公表した。加えて、メロテルペノイド構造複雑化に重要な役割を演じる環化酵素、酸素添加酵素、プレニル転移酵素、新規異性化酵素など、一連の酵素についても、同様に、酵素の精密機能解析と立体構造基盤の解明に成功した。
さらに、これらに加えて、インドールアルカロイド、スルホンアミド、ネオアンチマイシンなど、関連する一連の複雑骨格天然物の新規生合成マシナリーの構造機能解析、生合成リデザインにも成功し、研究成果を印刷公表した。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

  • Research Products

    (25 results)

All 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (20 results) (of which Int'l Joint Research: 15 results,  Peer Reviewed: 20 results,  Open Access: 8 results) Presentation (1 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] 中国科学院/浙江大学/武漢大学(中国)

    • Country Name
      CHINA
    • Counterpart Institution
      中国科学院/浙江大学/武漢大学
    • # of Other Institutions
      3
  • [Int'l Joint Research] ボストン大学/ペンシルバニア大学/スクリプス研究所(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      ボストン大学/ペンシルバニア大学/スクリプス研究所
  • [Int'l Joint Research] ボン大学(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      ボン大学
  • [Journal Article] One Polyketide Synthase, Two Distinct Products: Trans‐Acting Enzyme‐Controlled Product Divergence in Calbistrin Biosynthesis2021

    • Author(s)
      Tao Hui、Mori Takahiro、Wei Xingxing、Matsuda Yudai、Abe Ikuro
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 60 Pages: 8851~8858

    • DOI

      10.1002/anie.202016525

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chemistry of fungal meroterpenoid cyclases2021

    • Author(s)
      Barra Lena、Abe Ikuro
    • Journal Title

      Natural Product Reports

      Volume: 38 Pages: 566~585

    • DOI

      10.1039/D0NP00056F

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Enzymology and biosynthesis of the orsellinic acid derived medicinal meroterpenoids2021

    • Author(s)
      Tao Hui、Abe Ikuro
    • Journal Title

      Current Opinion in Biotechnology

      Volume: 69 Pages: 52~59

    • DOI

      10.1016/j.copbio.2020.11.016

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biosynthesis of alkyne-containing natural products2021

    • Author(s)
      Li Xinyang、Lv Jian-Ming、Hu Dan、Abe Ikuro
    • Journal Title

      RSC Chemical Biology

      Volume: 2 Pages: 166~180

    • DOI

      10.1039/D0CB00190B

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biosynthesis of sulfonamide and sulfamate antibiotics in Actinomycete2021

    • Author(s)
      Awakawa Takayoshi、Barra Lena、Abe Ikuro
    • Journal Title

      Journal of Industrial Microbiology and Biotechnology

      Volume: 48 Pages: -

    • DOI

      10.1093/jimb/kuab001

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microbial soluble aromatic prenyltransferases for engineered biosynthesis2021

    • Author(s)
      Chen He-Ping、Abe Ikuro
    • Journal Title

      Synthetic and Systems Biotechnology

      Volume: 6 Pages: 51~62

    • DOI

      10.1016/j.synbio.2021.02.001

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploiting the Potential of Meroterpenoid Cyclases to Expand the Chemical Space of Fungal Meroterpenoids2020

    • Author(s)
      Mitsuhashi Takaaki、Barra Lena、Powers Zachary、Kojasoy Volga、Cheng Andrea、Yang Feng、Taniguchi Yoshimasa、Kikuchi Takashi、Fujita Makoto、Tantillo Dean J.、Porco John A.、Abe Ikuro
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Pages: 23772~23781

    • DOI

      10.1002/anie.202011171

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exploiting a C-N Bond Forming Cytochrome P450 Monooxygenase for C-S Bond Formation2020

    • Author(s)
      Morita Iori、Mori Takahiro、Mitsuhashi Takaaki、Hoshino Shotaro、Taniguchi Yoshimasa、Kikuchi Takashi、Nagae Kei、Nasu Norihiro、Fujita Makoto、Ohwada Tomohiko、Abe Ikuro
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Pages: 3988~3993

    • DOI

      10.1002/anie.201916269

    • Peer Reviewed
  • [Journal Article] Heterochiral coupling in non-ribosomal peptide macrolactamization2020

    • Author(s)
      Matsuda Kenichi、Zhai Rui、Mori Takahiro、Kobayashi Masakazu、Sano Ayae、Abe Ikuro、Wakimoto Toshiyuki
    • Journal Title

      Nature Catalysis

      Volume: 3 Pages: 507~515

    • DOI

      10.1038/s41929-020-0456-7

    • Peer Reviewed
  • [Journal Article] Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides2020

    • Author(s)
      Kozakai Ryosuke、Ono Takuto、Hoshino Shotaro、Takahashi Hidenori、Katsuyama Yohei、Sugai Yoshinori、Ozaki Taro、Teramoto Kazuya、Teramoto Kanae、Tanaka Koichi、Abe Ikuro、Asamizu Shumpei、Onaka Hiroyasu
    • Journal Title

      Nature Chemistry

      Volume: 12 Pages: 869~877

    • DOI

      10.1038/s41557-020-0508-2

    • Peer Reviewed
  • [Journal Article] Biosynthesis of Biscognienyne?B Involving a Cytochrome P450‐Dependent Alkynylation2020

    • Author(s)
      Lv Jian‐Ming、Gao Yao‐Hui、Zhao Huan、Awakawa Takayoshi、Liu Ling、Chen Guo‐Dong、Yao Xin‐Sheng、Hu Dan、Abe Ikuro、Gao Hao
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 59 Pages: 13531~13536

    • DOI

      10.1002/anie.202004364

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases2020

    • Author(s)
      He Haibing、Bian Guangkai、Herbst-Gervasoni Corey J.、Mori Takahiro、Shinsky Stephen A.、Hou Anwei、Mu Xin、Huang Minjian、Cheng Shu、Deng Zixin、Christianson David W.、Abe Ikuro、Liu Tiangang
    • Journal Title

      Nature Communications

      Volume: 11 Pages: 3958-3958

    • DOI

      10.1038/s41467-020-17642-2

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea2020

    • Author(s)
      Zhang Yue-Hong、Li Yi-Fang、Wang Yongjin、Tan Li、Cao Zhi-Qin、Xie Chao、Xie Guo、Gong Hai-Biao、Sun Wan-Yang、Ouyang Shu-Hua、Duan Wen-Jun、Lu Xiaoyun、Ding Ke、Kurihara Hiroshi、Hu Dan、Zhang Zhi-Min、Abe Ikuro、He Rong-Rong
    • Journal Title

      Nature Communications

      Volume: 11 Pages: 1473-1473

    • DOI

      10.1038/s41467-020-15324-7

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural Diversification of Andiconin-Derived Natural Products by α-Ketoglutarate-Dependent Dioxygenases2020

    • Author(s)
      Bai Tongxuan、Matsuda Yudai、Tao Hui、Mori Takahiro、Zhang Yonghui、Abe Ikuro
    • Journal Title

      Organic Letters

      Volume: 22 Pages: 4311~4315

    • DOI

      10.1021/acs.orglett.0c01358

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sporormielones A?E, bioactive novel C?C coupled orsellinic acid derivative dimers, and their biosynthetic origin2020

    • Author(s)
      Chen Guo-Dong、Hu Dan、Huang Mei-Juan、Tang Jia、Wang Xiao-Xia、Zou Jian、Xie Jun、Zhang Wei-Guang、Guo Liang-Dong、Yao Xin-Sheng、Abe Ikuro、Gao Hao
    • Journal Title

      Chemical Communications

      Volume: 56 Pages: 4607~4610

    • DOI

      10.1039/D0CC00855A

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deciphering the Biosynthetic Mechanism of Pelletierine in Lycopodium Alkaloid Biosynthesis2020

    • Author(s)
      Wang Juan、Zhang Ze-Kun、Jiang Fang-Fang、Qi Bo-Wen、Ding Ning、Hnin Saw Yu Yu、Liu Xiao、Li Jun、Wang Xiao-hui、Tu Peng-Fei、Abe Ikuro、Morita Hiroyuki、Shi She-Po
    • Journal Title

      Organic Letters

      Volume: 22 Pages: 8725~8729

    • DOI

      10.1021/acs.orglett.0c03339

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Total Synthesis and Structural Revision of Kasumigamide, and Identification of a New Analogue2020

    • Author(s)
      Kuranaga Takefumi、Matsuda Kenichi、Takaoka Masachika、Tachikawa Chisato、Sano Ayae、Itoh Kosei、Enomoto Ayumu、Fujita Kei、Abe Ikuro、Wakimoto Toshiyuki
    • Journal Title

      ChemBioChem

      Volume: 21 Pages: 3329~3332

    • DOI

      10.1002/cbic.202000409

    • Peer Reviewed
  • [Journal Article] Molecular Basis for Sesterterpene Diversity Produced by Plant Terpene Synthases2020

    • Author(s)
      Chen Qingwen、Li Jianxu、Liu Zhixi、Mitsuhashi Takaaki、Zhang Yuting、Liu Haili、Ma Yihua、He Juan、Shinada Tetsuro、Sato Tsutomu、Wang Yong、Liu Hongwei、Abe Ikuro、Zhang Peng、Wang Guodong
    • Journal Title

      Plant Communications

      Volume: 1 Pages: 100051~100051

    • DOI

      10.1016/j.xplc.2020.100051

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enzymatic Formation of Indolactam Scaffold by C-N Bond‐Forming Cytochrome P450 Oxidases in Teleocidin Biosynthesis2020

    • Author(s)
      Morita Iori、Mori Takahiro、Abe Ikuro
    • Journal Title

      Chemistry A European Journal

      Volume: 27 Pages: 2963~2972

    • DOI

      10.1002/chem.202003899

    • Peer Reviewed
  • [Journal Article] Extensive expanding the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy2020

    • Author(s)
      Song Xiaojun、Lv Jianming、Cao Zhiqin、Huang Huiyun、Chen Guodong、Awakawa Takayoshi、Hu Dan、Gao Hao、Abe Ikuro、Yao Xinsheng
    • Journal Title

      Acta Pharmaceutica Sinica B

      Volume: 10 Pages: -

    • DOI

      10.1016/j.apsb.2020.12.007

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 非ヘム鉄-αケトグルタル酸依存性酸化酵素に関する研究2020

    • Author(s)
      阿部郁朗
    • Organizer
      第22回 生体触媒シンポジウム
    • Invited
  • [Remarks] 東京大学大学院薬学系研究科天然物化学教室

    • URL

      http://www.f.u-tokyo.ac.jp/~tennen/head.htm

URL: 

Published: 2021-12-27  

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