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Structure-based engineering of type-III polyketide synthase

Research Project

Project/Area Number 21710235
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Living organism molecular science
Research InstitutionThe University of Tokyo

Principal Investigator

MORITA Hiroyuki  The University of Tokyo, 大学院・薬学系研究科, 助教 (20416663)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords生合成 / ポリケタイド合成酵素 / タンパク工学 / ポリフェノール / アルカロイド / クルクミン / テトラミン酸 / ベンザルアセトン / カルコン
Research Abstract

We solved crystal structures of benzalacetone synthase (BAS) from Rheum palmatum, curcuminoid synthase (CUS) from Oryza sativa and polyketide synthase (HsPKS) from Hupersia serrata. Furthermore, by carrying out the structure-based site-directed mutagenesis studies, we succeeded to add a new function against CUS and HsPKS, respectively. We also revealed that BAS produces tetramic acid derivatives from a condensation of aminoacyl-CoA with malonyl-CoA.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2011 2010 2009

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (26 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Molecular Cloning, Modeling and Site-directed Mutagenesis of Type III Polyketide Synthase from Sargassum binderi (Phaeophyta)2011

    • Author(s)
      Hariyanti Baharum, Hiroyuki Morita, Akifumi. Tomitsuka, Fong-Chin Lee, Kim-Yong Ng, Raha Abdul Rahim, Ikuro Abe, Chai-Ling Ho
    • Journal Title

      Marine Biotechnology. In press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic Tetramic Acid Derivative Produced by A Plant Type-III Polyketide Synthase2011

    • Author(s)
      Toshiyuki Wakimoto, Takahiro Mori, Hiroyuki Morita, Ikuro Abe
    • Journal Title

      J.Am.Chem.Soc. 67

      Pages: 409-411

    • NAID

      10029237041

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enzymatic Formation of An Aromatic Dodecaketide by Engineered Plant Polyketide Synthase2011

    • Author(s)
      Kiyofumi Wanibuchi, Hiroyuki Morita, Hiroshi Noguchi, Ikuro Abe
    • Journal Title

      Bioorg.Med.Chem.Lett. 21

      Pages: 2083-2086

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and Preliminary X-ray Analysis of 4-Coumarate : CoA Ligase from Arabidosis thaliana2011

    • Author(s)
      Hiroyuki Morita, Takahiro Mori, Kiyofumi Wanibuchi, Ryohei Kato, Shigetoshi Sugio, Ikuro Abe
    • Journal Title

      Acta Cryst. F67

      Pages: 409-411

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic tetramic acid derivative produced by a plant type-III polyketide synthase2011

    • Author(s)
      Toshiyuki Wakimoto, Takahiro Mori, Hiroyuki Morita, Ikuro Abe
    • Journal Title

      J.Am.Chem.Soc.

      Volume: (印刷中)(掲載確定)

    • NAID

      10029237041

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning, modeling and site-directed mutagenesis of type III polyketide synthase form Sargassum binderi (Phaeophyta)2011

    • Author(s)
      Hariyanti Baharum, Hiroyuki Morita, Akifumi Tomitsuka, Fong-Chin Lee, Kim-Yong Ng, Raha Abdul Rahim, Ikuro Abe, Chai-Ling Ho
    • Journal Title

      Marine Biotechnology

      Volume: (印刷中)(掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 二次代謝酵素の機能制御と生合成工学2011

    • Author(s)
      森田洋行、阿部郁朗
    • Journal Title

      化学工業

      Volume: Vol.62 Pages: 14-20

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression, Purification and Crystallization of A Plant Type III Polyketide Synthase that Produces Curcuminoid2011

    • Author(s)
      Kiyofumi Wanibuchi, Hiroyuki Morita, Hiroshi Noguchi, Ikuro Abe
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: VOL.21 Pages: 2083-2086

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa2010

    • Author(s)
      Hiroyuki Morita, Kiyofumi Wanibuchi, Hirohiko Nii, Ryohei Kato, Shigetoshi Sugio, Ikuro Abe
    • Journal Title

      Proc.Natl.Acad.Sci.USA 107

      Pages: 19778-19783

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure-based Engineering of Benzalacetone Synthase2010

    • Author(s)
      Yoshihiko Shimokawa, Hiroyuki Morita, Ikuro Abe
    • Journal Title

      Bioorg.Med.Chem.Lett. 20

      Pages: 5099-5103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression, Purification and Crystallization of A Plant Type III Polyketide Synthase that Produces Curcuminoid2010

    • Author(s)
      Hiroyuki Morita, Kiyofumi Wanibuchi, Ryohei Kato, Shigetoshi Sugio, Ikuro Abe
    • Journal Title

      Acta Cryst. F66

      Pages: 948-950

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure and Function of The Chalcone Synthase Superfamily of Plant TypeIII Polyketide Synthases2010

    • Author(s)
      Ikuro Abe, Hiroyuki Morita
    • Journal Title

      Nat.Prod.Rep. 27

      Pages: 809-838

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Structure-based Mechanism for Benzalacetone Synthase from Rheum palmatum2010

    • Author(s)
      Hiroyuki Morita, Yoshihiko Shimokawa, Michikazu Tanio, Ryohei Kato, Hiroshi Noguchi, Shigetoshi Sugio, Toshiyuki Kohno, Ikuro Abe
    • Journal Title

      Proc.Natl.Acad.Sci.USA 107

      Pages: 669-673

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase2010

    • Author(s)
      Hiroyuki Morita, Kiyofumi Wanibuchi, Hirohiko Nii, Ryohei Kato, Shigetoshi Sugio
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: VOL.107 Pages: 19778-19783

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-based engineering of benzalacetone synthase2010

    • Author(s)
      Yoshihiko Shimokawa, Hiroyuki Morita, Ikuro Abe
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: VOL.20 Pages: 5099-5103

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression, Purification and Crystallization of A Plant Type III Polyketide Synthase that Produces Curcuminoid2010

    • Author(s)
      Hiroyuki Morita, Kiyofumi Wanibuchi, Ryohei Kato, Shigetoshi Sugio, Ikuro Abe
    • Journal Title

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

      Volume: VOL.67 Pages: 948-950

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and Function of The Chalcone Synthase Superfamily of Plant TypeIII Polyketide Synthases2010

    • Author(s)
      Ikuro Abe, Hiroyuki Morita
    • Journal Title

      Nat.Prod.Rep. (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 植物ポリケタイド合成酵素研究の最前線2009

    • Author(s)
      森田洋行、阿部郁朗
    • Journal Title

      化学と生物 47

      Pages: 772-780

    • NAID

      10026436926

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Structure-based Mechanism for Benzalacetone Synthase from Rheum palmatum2009

    • Author(s)
      Hiroyuki Morita, Yoshihiko Shimokawa, Michikazu Michikazu, Ryohei Kato, Hiroshi Noguchi, Shigetoshi Sugio, Toshiyuki Kohno, Ikuro Abe
    • Journal Title

      Proc.Natl.Acad.Sci.USA VOL.107

      Pages: 669-673

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 植物ポリケタイド合成酵素研究の最前線2009

    • Author(s)
      森田洋行、阿部郁朗
    • Journal Title

      化学と生物 VOL.47

      Pages: 772-780

    • NAID

      10026436926

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] A Structure-based Mechanisms for Plant Polyketide Biosynthesis2011

    • Author(s)
      森田洋行
    • Organizer
      JSPS-DGHE JOINT RESERCH PORJECT
    • Place of Presentation
      Bandung (Indonesia)
    • Year and Date
      2011-01-18
    • Related Report
      2010 Final Research Report
  • [Presentation] A Structure-based Mechanisms for Plant Polyketide Biosynthesis2011

    • Author(s)
      森田洋行
    • Organizer
      JSPS-DGHE JOINT RESERCH PORJECT
    • Place of Presentation
      Bandung、Indonesia
    • Year and Date
      2011-01-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Structure-based mechanism for benzalacetone synthase from Rheum palmatum2010

    • Author(s)
      森田洋行、下川良彦、阿部郁朗
    • Organizer
      PACIFICHEM2010
    • Place of Presentation
      Hawaii (USA)
    • Year and Date
      2010-12-17
    • Related Report
      2010 Final Research Report
  • [Presentation] Structure-based mechanism for benzalacetone synthase from Rheum palmatum2010

    • Author(s)
      森田洋行、下川良彦、阿部郁朗
    • Organizer
      PACIFICHEM2010
    • Place of Presentation
      Hawaii、USA
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Enzymatic formation of unnatural novel chalcone, stilbene, and benzophenone scaffolds by plant type III polyketide synthase2010

    • Author(s)
      鰐渕清史、Shepo-Shi Shi、森田洋行、野口博司、阿部郁朗
    • Organizer
      PACIFICHEM2010
    • Place of Presentation
      Hawaii、USA
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cloning and characterization of novel type III polyketide synthases from calamondin orange (Citrus microcarpaBunge)2010

    • Author(s)
      金城桂史、森田洋行、野口博司、阿部郁朗
    • Organizer
      PACIFICHEM2010
    • Place of Presentation
      Hawaii、USA
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Enzymatic synthesis of unnatural novel alkaloidal scaffolds by plant polyketide syntheses2010

    • Author(s)
      山下誠、森田洋行、Shepo Shi、野口博司、阿部郁朗
    • Organizer
      PACIFICHEM2010
    • Place of Presentation
      Hawaii、USA
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 植物ポリケタイド合成酵素の構造と機能2010

    • Author(s)
      森田洋行
    • Organizer
      第47回植物化学シンポジウム
    • Place of Presentation
      静岡県立大学(静岡県)
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Crystal Structure Analysis of The Type III Polyketide Synthase That Produces Curcuminoid2010

    • Author(s)
      森田洋行、阿部郁朗
    • Organizer
      25^<th> Symposium on Natural Products
    • Place of Presentation
      Tainan (Taiwan)
    • Year and Date
      2010-11-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Crystal structure analysis of the type III polyketide synthase that produces curcuminoid2010

    • Author(s)
      森田洋行、阿部郁朗
    • Organizer
      第25回天然薬物検討会
    • Place of Presentation
      国立海洋生物博物館行政中心国際会議棟(台北、台湾)
    • Year and Date
      2010-11-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 植物ポリケタイド合成酵素の触媒機能の拡張と非天然型化合物の創出2010

    • Author(s)
      森田洋行
    • Organizer
      第3回日本薬学会関東支部若手シンポジウム
    • Place of Presentation
      東京薬科大学(東京都)
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] クマロイルCoA合成酵素の新規触媒機能と構造解析:チオエステルからアミドリガーゼ、ペプチド合成酵素への機能拡張2010

    • Author(s)
      鰐渕清史、森貴裕、庭野智子、張剛、脇本敏幸、森田洋行、阿部郁朗
    • Organizer
      第52回天然有機化合物討論会
    • Place of Presentation
      グランシップ静岡(静岡県)
    • Year and Date
      2010-09-29
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 植物ポリフェノールの生合成に関する研究2010

    • Author(s)
      森田洋行
    • Organizer
      第57回日本生薬学会年会
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2010-09-26
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 光学活性アミノ酸誘導体を基質とした植物ポリケタイド合成酵素の触媒機能拡張2010

    • Author(s)
      森貴裕、森田洋行、脇本敏幸、阿部郁朗
    • Organizer
      第57回日本生薬学会年会
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] ポリケタイド合成酵素のX線結晶構造解析を基盤とする新規アルカロイド骨格合成反応機構の解明2010

    • Author(s)
      森田洋行、山下誠、野口博司、脇本敏幸、阿部郁朗
    • Organizer
      第57回日本生薬学会年会
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 四季柑由来キノリノンの骨格を構築する新規III型ポリケタイド合成酵素のクローニングと機能解析2010

    • Author(s)
      金城桂史、森田洋行、野口博司、阿部郁朗
    • Organizer
      第57回日本生薬学会年会
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] クマロイルCoA合成酵素の新規触媒機能の開拓2010

    • Author(s)
      鰐渕清史、森田洋行、阿部郁朗
    • Organizer
      第57回日本生薬学会年会
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] クマロイルCoA合成酵素の新規触媒機能と構造解析:チオエステルからアミドリガーゼ、ペプチド合成酵素への機能拡張2010

    • Author(s)
      鰐渕清史、庭野智子、脇本敏幸、森田洋行、阿部郁朗
    • Organizer
      第14回生体触媒化学シンポジウム
    • Place of Presentation
      グランシップ静岡(静岡県)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] III型ポリケタイド合成酵素を用いた非天然型新規アルカロイドの創出2010

    • Author(s)
      森貴裕、森田洋行、阿部郁朗
    • Organizer
      第45回天然物化学談話会
    • Place of Presentation
      三谷温泉ホテル明山荘(愛知県)
    • Year and Date
      2010-07-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 結晶構造に基づく植物ポリケタイド合成酵素の反応機構の解明2010

    • Author(s)
      森田洋行、下川良彦、加藤良平、杉尾成俊、河野俊之、阿部郁朗
    • Organizer
      第10回日本蛋白質科学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 植物ポリケタイド合成酵素の機能制御と超天然型新規生体触媒の開発2010

    • Author(s)
      森田洋行
    • Organizer
      第11回酵素応用シンポジウム
    • Place of Presentation
      メルパルクNAGOYA(愛知県)
    • Year and Date
      2010-06-11
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 植物ポリケタイド合成酵素の潜在的触媒能力を活用した非天然型新規アルカロイド骨格の創出2009

    • Author(s)
      山下誠、鰐渕清史、史社坡、森田洋行、野口博司、阿部郁朗
    • Organizer
      第51回天然有機化合物討論会
    • Place of Presentation
      名古屋市公会堂(愛知県)
    • Year and Date
      2009-10-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 植物ポリケタイド合成酵素の潜在的触媒能力を活用した非天然型新規アルカロイド骨格の創出2009

    • Author(s)
      山下誠, 鰐渕清史, 史社坡, 森田洋行, 野口博司, 阿部郁朗
    • Organizer
      第51回 天然有機化合物討論会
    • Place of Presentation
      名古屋市公会堂(愛知県)
    • Year and Date
      2009-10-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] 植物ポリケタイド合成酵素のX線結晶構造解析と新たな酵素触媒機能の開拓2009

    • Author(s)
      森田洋行
    • Organizer
      第44回天然物化学談話会
    • Place of Presentation
      つくばグランドホテル(茨城県)
    • Year and Date
      2009-07-09
    • Related Report
      2010 Final Research Report
  • [Presentation] 植物ポリケタイド合成酵素のX線結晶構造解析と新たな酵素触媒機能の開拓2009

    • Author(s)
      森田洋行
    • Organizer
      第44回 天然物化学談話会
    • Place of Presentation
      つくばグランドホテル(茨城県)
    • Year and Date
      2009-07-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Structure and function of benzalacetone synthase2009

    • Author(s)
      Jing Chen, Hiroyuki Morita, Hiroshi Noguchi, Shigetoshi Sugio, Toshiyuki Kohno, Ikuro Abe
    • Organizer
      The 50^<th> Anniversary Meeting of the American Society of Pharmacognosy
    • Place of Presentation
      Sheratone Waikiki Hotel(Hawaii)
    • Year and Date
      2009-06-27
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 植物ポリケタイド合成酵素を用いた3環性非天然型アルカロイドの生産2010

    • Inventor(s)
      阿部郁朗、脇本敏幸、森田洋行、山下誠
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Filing Date
      2010-09-22
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 植物ポリケタイド合成酵素を用いた6-7-6縮合環構造を有する3環性非天然型アルカロイドの生産2010

    • Inventor(s)
      阿部郁朗、脇本敏幸、森田洋行、山下誠
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Number
      2010-212208
    • Filing Date
      2010-09-22
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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