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Engineering of plant-specific polyketide scaffold synthetic enzymes to produce structural diversity of compounds

Research Project

Project/Area Number 26282210
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biomolecular chemistry
Research InstitutionUniversity of Toyama

Principal Investigator

Morita Hiroyuki  富山大学, 和漢医薬学総合研究所, 教授 (20416663)

Co-Investigator(Renkei-kenkyūsha) MATSUI Takashi  富山大学, 和漢医薬学総合研究所, 助教 (30463582)
KODAMA Takeshi  富山大学, 和漢医薬学総合研究所, 特命助教 (40710207)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywordsポリケタイド / 酵素工学 / X線結晶構造解析 / 閉環酵素 / 立体構造解析 / アルカロイド
Outline of Final Research Achievements

In order to produce structural diversity of compounds, combinatorial biosyntheses of the polyketide cyclase, olivetolic acid cyclase (OAC) and the type III polyketide synthase, octaketide synthase from Aloe arborescens using structurally distinct various CoA thioesters as the substrates were carried out. As a result, we found that the co-incubation of the enzymes using hexanoyl-CoA and malonyl-CoA as the substrates led to a production of novel naphthalene. Furthermore, we solved OAC apo and OAC-olivetolic acid binary complex structures at 1.4 angstrom and 1.7 angstrom resolutions, respectively. The crystallographic and site-directed mutagenesis studies of OAC revealed that the enzyme possesses the pentyl-binding pocket that plays an important role to bind the pentyl moiety of the substrate and employs Tyr72 and His78 as the catalytic residues.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (49 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results,  Open Access: 6 results,  Acknowledgement Compliant: 10 results) Presentation (32 results) (of which Int'l Joint Research: 11 results,  Invited: 11 results) Remarks (1 results)

  • [Int'l Joint Research] Hasanuddin University(Indonesia)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action2017

    • Author(s)
      T. Matsui, S. Lallo, K. Nisa, H. Morita.
    • Journal Title

      Bioorg Med Chem Lett

      Volume: 27 Issue: 6 Pages: 1420-1424

    • DOI

      10.1016/j.bmcl.2017.01.095

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A novel class of plant type III polyketide synthase involved in orsellinic acid biosynthesis from Rhododendron dauricum2016

    • Author(s)
      F. Taura, M. Iijima, E. Yamanaka, H. Takahashi, H. Kenmoku, H. Saeki, S. Morimoto, Y. Asakawa, F. Kurosaki, H. Morita.
    • Journal Title

      Front Plant Sci

      Volume: 7 Pages: 1452-1452

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural insight into the enzymatic formation of bacterial stilbene2016

    • Author(s)
      Mori, T., Awakawa, T., Shimomura, K., Saito, Y., Yang, D., Morita, H., Abe, I.
    • Journal Title

      Cell Chem. Biol.

      Volume: 23 Issue: 12 Pages: 1468-1479

    • DOI

      10.1016/j.chembiol.2016.10.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Manipulation of prenylation reactions by structure-based engineering of bacterial indolactam prenyltransferases2016

    • Author(s)
      T. Mori, L. Zhang, T. Awakawa, S. Hoshino, M. Okada, H. Morita, I. Abe
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 10849-10851

    • DOI

      10.1038/ncomms10849

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structural basis for olivetolic acid formation by a polyketide cyclase from Cannabis sativa2016

    • Author(s)
      X. Yang, T. Matsui, T. Kodama, T. Mori, X. Zhou, F. Taura, H. Noguchi, I. Abe, H. Morita
    • Journal Title

      FEBS J

      Volume: 283 Issue: 6 Pages: 1088-1106

    • DOI

      10.1111/febs.13654

    • NAID

      120006559813

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural basis for the β-carboline alkaloids production by the microbial homodimeric enzyme McbB2015

    • Author(s)
      T. Mori, S. Hoshino, S. Sahashi, T. Wakimoto, T. Matsui, H. Morita, I. Abe
    • Journal Title

      Chem. Biol.

      Volume: 17 Issue: 7 Pages: 1501-1504

    • DOI

      10.1016/j.chembiol.2015.06.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Expression, purification, and crystallization of a plant polyketide cyclase from Cannabis sativa2015

    • Author(s)
      X. Yang, T. Matsui, T. Mori, F. Taura, H. Noguchi, I. Abe, H. Morita
    • Journal Title

      Acta Crystallographica Section F

      Volume: 71 Issue: 12 Pages: 1470-1474

    • DOI

      10.1107/s2053230x15020385

    • NAID

      120006389597

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin.2015

    • Author(s)
      Noike, M., Matsui, T., Ooya, K., Sasaki, I., Ohtaki, S., Hamano, Y., Maruyama, C., Ishikawa, J., Satoh, Y., Ito, H., Morita, H. and Dairi T.
    • Journal Title

      Nature Chemical Biology

      Volume: 11 Issue: 1 Pages: 71-76

    • DOI

      10.1038/nchembio.1697

    • NAID

      120005619608

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structural basis for the formation of acylalkylpyrones from two β-ketoacyl units by the fungal type III polyketide synthase CsyB2015

    • Author(s)
      Mori, T., Yang, D., Matsui, T, Hashimoto, M., Morita, H., Fujii, I., Abe, I.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 8 Pages: 5214-5225

    • DOI

      10.1074/jbc.m114.626416

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Preferential cytotoxicity of crude drugs used in Japanese Kampo medicines against human pancreatic cancer PANC-1 and PSN-1 cells2015

    • Author(s)
      S. Lee, D.F. Dibwe, F. Li, H. Morita, Y. Tezuka
    • Journal Title

      Traditional & Kampo Medicine

      Volume: なし Issue: 2 Pages: 1-8

    • DOI

      10.1002/tkm2.1016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preferential cytotoxic constituents of Andrographis paniculata and their preferential cytotoxicity against human pancreatic cancer cell lines2015

    • Author(s)
      S. Lee, H. Morita, Y. Tezuka
    • Journal Title

      Nat. Prod. Comm.

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression, purification, and crystallization of a fungal type III polyketide synthase that produces the csypyrones2014

    • Author(s)
      Yang, D., Mori, T., Matsui, T., Hashimoto, M., Morita, H., Fujii, I., Abe, I.
    • Journal Title

      Acta Crystallogr., Sect. F: Struct. Biol. Cryst. Commun.

      Volume: 70 Issue: 6 Pages: 730-733

    • DOI

      10.1107/s2053230x14008516

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Muchimangins G-J, Fully Substituted Xanthones with a Diphenylmethyl Substituent, from Securidaca longepedunculata2014

    • Author(s)
      D.F. Dibwe, S. Awale, S. Kadota, H. Morita, Y. Tezuka
    • Journal Title

      J. Nat. Prod.

      Volume: 77 Issue: 5 Pages: 1241-1244

    • DOI

      10.1021/np5000445

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda and their cytotoxic activity2014

    • Author(s)
      Subehan, S. Lee, D.F. Dibwe, Y. Tezuka, H. Morita
    • Journal Title

      Nat. Prod. Res.

      Volume: 28 Issue: 20 Pages: 1754-1759

    • DOI

      10.1080/14786419.2014.945175

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phytochemical investigation of the active constituents from <i>Caesalpinia sappan</i> on stimulation of osteoblastic cells2014

    • Author(s)
      Subehan, Y. Rifai, Mufidah, Ismail, M. Aswad, H. Morita
    • Journal Title

      Plant Biotechnology

      Volume: 31 Issue: 5 Pages: 505-509

    • DOI

      10.5511/plantbiotechnology.14.0911a

    • NAID

      130005129277

    • ISSN
      1342-4580, 1347-6114
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Manipulation of plant polyketide-producing enzymes to produce new compounds2016

    • Author(s)
      H. Morita
    • Organizer
      The 1st International Conference on Environmental Science and Pollution for 96th Anniversary of University of Yangon
    • Place of Presentation
      Yangon, Myanmar
    • Year and Date
      2016-12-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structure basis for novel plant polyketide cyclase2016

    • Author(s)
      H. Morita
    • Organizer
      The 6th International Symposium in Phyochemicals-Bioactivities and Disease Preventation of Phyochemicals and Natural Produts for Health
    • Place of Presentation
      Chiayi, Taiwan
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アサ由来ポリケタイド閉環酵素のポリケタイド閉環機構の解明2016

    • Author(s)
      松井崇,楊新美,周暁希,児玉猛,森貴裕,野口博司,阿部郁朗,森田洋行
    • Organizer
      日本結晶学会平成28年度年会および会員総会
    • Place of Presentation
      水戸
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of plant polyketide-producing enzymes to produce new compounds2016

    • Author(s)
      H. Morita
    • Organizer
      International Meeting 2016 of the Plant Resources Society of Korea
    • Place of Presentation
      Jecheon, Korea
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Crystal structure analysis of novel plant cyclase2016

    • Author(s)
      H. Morita
    • Organizer
      Korea-China-Japan Joint Symposium in Pharmaceutical Sciences
    • Place of Presentation
      Jecheon, Korea
    • Year and Date
      2016-09-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 植物ポリケタイド骨格形成酵素群の機能多様性に関する研究2016

    • Author(s)
      森田洋行
    • Organizer
      第63回日本生薬学会年会
    • Place of Presentation
      富山
    • Year and Date
      2016-09-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Prenylation of alkaloids by exploiting indole prenyltransferase for drug discovery2016

    • Author(s)
      H. Morita
    • Organizer
      55th Anniversary of National Institute of Medicinal Material Conference
    • Place of Presentation
      Hanoi, Vietnam
    • Year and Date
      2016-04-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アサ由来ポリケタイド閉環酵素のX線結晶構造解析2016

    • Author(s)
      森田洋行,楊新美,松井崇,児玉猛,森貴裕,周暁希,野口博司,阿部郁朗
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Crystal structure analysis of the novel plant polyketide cyclase2016

    • Author(s)
      Morita H
    • Organizer
      International Conference on Natural Products (ICNP) 2016
    • Place of Presentation
      Kuala Terengganu, Malaysia
    • Year and Date
      2016-03-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アサ由来ポリケタイド閉環酵素のX線結晶構造解析2016

    • Author(s)
      松井崇,楊新美,児玉猛,周暁希,森貴裕,野口博司,阿部郁朗,森田洋行
    • Organizer
      2015年度量子ビームサイエンスフェスタ
    • Place of Presentation
      つくば
    • Year and Date
      2016-03-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Structural basis for novel plant polyketide cyclase2016

    • Author(s)
      Morita H
    • Organizer
      32nd International Annual Meeting in Pharmaceutical Sciences
    • Place of Presentation
      Chulalongkorn, Thailand
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structure-function analyses of two novel plant type III polyketide synthases obtained from medicinal plant Evodia rutaecarpa2015

    • Author(s)
      Kodama T., Matsui T., Mori T., Tadakoshi T., Noguchi H., Abe I., Morita H
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Precursor-directed biosynthesis of unnatural novel alkaloids by using a plant type III polyketide synthase obtained from Evodia rutaecarpa2015

    • Author(s)
      Ito T., Kodama T., Noguchi H., Abe I., Morita H
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of two novel plant type III polykeitde synthases obtained from medicinal plant Evodia rutaecarpa2015

    • Author(s)
      Morita H
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アサ由来ポリケタイド閉環酵素のX線結晶構造解析2015

    • Author(s)
      森田洋行,楊新美,松井崇,児玉猛,周暁希,森貴裕,野口博司,阿部郁朗
    • Organizer
      酵素工学研究会第74回講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Structural basis of polyketide cyclase from Cannabis sativa2015

    • Author(s)
      Yang X., Matsui T., Kodama T., Abe I., Morita H.: Structural basis of polyketide cyclase from Cannabis sativa
    • Organizer
      ISPSA2015
    • Place of Presentation
      Tokushima
    • Year and Date
      2015-08-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 植物ポリケタイド骨格形成酵素群を利用した非天然型化合物群の創出2015

    • Author(s)
      森田洋行
    • Organizer
      理研NMR天然物シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ゴシュユ由来新規Ⅲ型ポリケタイド合成酵素のcDNAクローニングと機能解析2015

    • Author(s)
      児玉猛、野口博司、阿部郁朗、森田洋行
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 穿心蓮中の栄養飢餓状態選択的な殺細胞活性成分2015

    • Author(s)
      李 雪林、森田洋行、手塚康弘
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規ジアルキル縮合酵素のX線結晶構造解析2015

    • Author(s)
      森貴裕、齋藤友理、下村康一郎、脇本敏幸、森田洋行、阿部郁朗
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] New secondary metabolites, Kaempuchraols A-J from Rhizomes of Kaempferia pulchra and their antiproliferative activity2015

    • Author(s)
      Win Nwet Nwet、Ito Takuya、Aimaiti Simayijing、Morita Hiroyuki
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crystal structure analysis of the secondary metabolite enzymes promoted the production of new compounds for drug discovery2014

    • Author(s)
      森田洋行
    • Organizer
      2014 Joint symposium of The Natural Prodcuts Research Institute at Seoul National University & The Institute of Natural Medicine at University of Toyama
    • Place of Presentation
      韓国 ソウル
    • Year and Date
      2014-12-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] インドールプレニル基転移酵素の動的立体構造基盤の確立と酵素触媒機能の拡張2014

    • Author(s)
      森田洋行
    • Organizer
      新学術領域研究生合成マシナリー 第8回公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] インドネシア産Caesalpinia sappanからの骨芽細胞増殖促進活性成分の探索2014

    • Author(s)
      Subehan、Rifai Y、Mufidah、Ismail、Aswad M、森田洋行
    • Organizer
      第20会天然薬物の開発と応用シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-11-05 – 2014-11-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] ペプチド系抗生物質フェガノマイシンの生合成に見いだされた新規ペプチドライゲース PGM1 の結晶構造解析2014

    • Author(s)
      松井崇、大瀧翔太、野池基義、大利徹、森田洋行
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] リボソームと新規ペプチドライゲースによる協同的ペプチド生成機構2014

    • Author(s)
      野池基義、松井崇、雄谷洸一、笹木郁雄、丸山千登勢、濱野吉一、石川淳、佐藤康治、伊藤肇、森田洋行、大利徹
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Teleocidin類の生合成機構の解明2014

    • Author(s)
      森貴裕、淡川孝義、張驪駻、星野翔太郎、脇本敏幸、森田洋行、伊藤卓也、石川淳、阿部郁朗
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda and their cytotoxic activity2014

    • Author(s)
      Subehan, Hiroyuki Morita
    • Organizer
      The 8th JSP-CCTCNM-KSP Joint Symposium on Pharmacognosy
    • Place of Presentation
      福岡
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] インドールプレニル基転移酵素の動的立体構造基盤の確立と酵素触媒機能の拡張2014

    • Author(s)
      森田洋行
    • Organizer
      新学術領域研究生合成マシナリー 第7回公開シンポジウム
    • Place of Presentation
      神奈川
    • Year and Date
      2014-06-21 – 2014-06-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 放線菌由来新規Pictet-Spengler反応触媒酵素McbBの構造機能解析2014

    • Author(s)
      佐橋周作、森貴裕、森田洋行、阿部郁朗
    • Organizer
      第29回年度日本放線菌学会
    • Place of Presentation
      筑波
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 放線菌由来新規インドールプレニルトランスフェラーゼTldCとMpnDのX線結晶構造解析2014

    • Author(s)
      森貴裕、張驪駻、淡川孝義、脇本敏幸、森田洋行、阿部郁朗
    • Organizer
      第29回年度日本放線菌学会
    • Place of Presentation
      筑波
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 放線菌に見いだされた新規ペプチドライゲースは幅広い基質特異性を持つ2014

    • Author(s)
      野池基義、松井崇、佐藤康治、森田洋行、大利徹
    • Organizer
      第29回年度日本放線菌学会
    • Place of Presentation
      筑波
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Remarks] 富山大学和漢医薬学総合研究所 天然物化学分野

    • URL

      http://www.inm.u-toyama.ac.jp/napc/index.html

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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