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Unification of biosynthetic pathways of a variety of plant polyketides

Research Project

Project/Area Number 25242067
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionUniversity of Shizuoka

Principal Investigator

Noguchi Hiroshi  静岡県立大学, 薬学部, 教授 (60126141)

Co-Investigator(Kenkyū-buntansha) MORITA HIROYUKI  富山大学, 和漢医薬学総合研究所, 教授 (20416663)
UMEHARA KAORU  静岡県立大学, 薬学部, 講師 (40185070)
WATANABE KENJI  静岡県立大学, 薬学部, 教授 (50360938)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000)
Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2014: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2013: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Keywordsポリケタイド / 生合成 / 反応機構 / タンパク質結晶構造解析 / 植物 / 酵素工学 / 閉環酵素 / X線結晶構造解析 / Type III PKS / polyketide synthase / OAC
Outline of Final Research Achievements

We showed the possibility that tyrosine 72 and histidine 78 was a catalyst residue of OAC from analysis and a variation introduction experiment of the complex X-rays crystal structure with the Oribe Thor acid which was Oribe Thor acid closure enzyme (OAC) derived from hemp and the product. Furthermore, We clarified what enzyme activity attenuated when bulky substituted the amino acid residue which formed a pentyl-binding pocket full of the hydrophobicity that we found in an active site of OAC for a higher bulky residue. Based on the X-ray crystallographic analysis about these variation enzymes, the capacity of the pentyl-binding pocket decreased by introduction of the variation, and a substrate became hard to be connected, it became clear to attenuate enzyme activity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (30 results)

All 2016 2015 2014 2013 Other

All Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 18 results,  Acknowledgement Compliant: 8 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results)

  • [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: 1 Pages: 1-6

    • 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
  • [Journal Article] Muchimangins E and F: novel diphenylmethyl-substituted xanthones from Securidaca longepedunculata2014

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Tetrahedron Lett.

      Volume: 55 Issue: 11 Pages: 1916-1919

    • DOI

      10.1016/j.tetlet.2014.01.149

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from Citrus microcarpa2013

    • Author(s)
      Mori, T., Shimokawa, Y., Matsui, T., Kinjo, K., Kato, R., Noguchi, H., Sugio, S., Morita, H., Abe, I.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 40 Pages: 28845-28858

    • DOI

      10.1074/jbc.m113.493155

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heptaoxygeneted xanthones as anti-austerity agents from Securidaca longepedunculata2013

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 21 Issue: 24 Pages: 7663-7668

    • DOI

      10.1016/j.bmc.2013.10.027

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spiro-carbon formation by different chemistry involving pathway crosstalk.2013

    • Author(s)
      石川格靖, 他8名
    • Journal Title

      Nature Chemical Biology

      Volume: 9 Issue: 12 Pages: 818-825

    • DOI

      10.1038/nchembio.1366

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted disruption of transcriptional regulators in Chaetomium globosum activates biosynthetic pathways and reveals transcriptional regulator-like behavior of aureonitol.2013

    • Author(s)
      Nakazawa T, et al.
    • Journal Title

      J. Am. Chem. Soc

      Volume: 135 Issue: 36 Pages: 13446-13455

    • DOI

      10.1021/ja405128k

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combinatorial Generation of Complexity by Redox Enzymes in the Chaetoglobosin A Biosynthesis2013

    • Author(s)
      K. Ishiuchi, T. Nakazawa, F. Yagishita, T. Mino, H. Noguchi, K.a Hotta, K. Watanabe
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 135 Issue: 19 Pages: 7371-7377

    • DOI

      10.1021/ja402828w

    • URL

      http://dx.doi.org/

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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
      横浜市
    • Year and Date
      2016-03-27
    • 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
    • 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
  • [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
    • Invited
  • [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] 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] New insight into substrate promiscuity and catalytic versatility of a fungal indole prenyltransferase2013

    • Author(s)
      Hiroyuki Morita,Ikuro Abe
    • Organizer
      Enzyme Engineering XXII: Emerging Topics in Enzyme Engineering
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Natural products from fungi2013

    • Author(s)
      Kenji Watanabe
    • Organizer
      3rd International Conference on Natural product Biosynthesis
    • Place of Presentation
      University of California Los Angeles, University of Southern California (USA)
    • Related Report
      2013 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

    • Author(s)
      森田洋行
    • Organizer
      新学術領域研究生合成マシナリー 第5回公開シンポジウム
    • Place of Presentation
      北海道大学(北海道札幌)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Engineering of plant type III polyketides synthase

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminar on Campus Asia Program University of Toyama 2013
    • Place of Presentation
      慶熙大学校(韓国ソウル)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Prenylation of polyketides and alkaloids by exploring indole prenyltransferase for drug discovery

    • Author(s)
      Hiroyuki Morita
    • Organizer
      International Conference on Medicinal Chemistry and Timmerman Award 2013 (ICMCTA2013)
    • Place of Presentation
      インドネシア大学(インドネシア・ジャカルタ)
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-15   Modified: 2019-07-29  

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