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Function analysis of a polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood

Research Project

Project/Area Number 20K16025
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionUniversity of Toyama

Principal Investigator

Takeshi Kodama  富山大学, 学術研究部薬学・和漢系, 助教 (40710207)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords沈香 / 生合成 / ポリケタイド合成酵素 / X線結晶構造解析 / ポリケタイド / 酵素工学 / X線結晶構造解析
Outline of Research at the Start

沈香は,高貴な香りのする高級香木として,中国や日本において用いられてきた。日本においては,お香としての需要が高い。さらに,中国や日本においては,精神作用を持つ生薬として中医薬や漢方医薬で用いられている。本研究では,沈香の芳香成分2-(2-フェニルエチル)クロモン類の産生に対応して発現する4つのⅢ型ポリケタイド合成酵素(PKS)遺伝子(AsPKS1~4)の触媒機能を同定することで,その芳香成分基本骨格の生合成の解明に取り組む。また,本研究では,これらの酵素に基質アナログを作用させることで,非天然型新規化合物の創出にも取り組む。

Outline of Final Research Achievements

2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. In this work, we describe a type III polyketide synthase (PECPS) identified from Aquilaria sinensis. We demonstrate that the scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure analyses of PECPS employs a one-pot formation mechanism for the formation of the diarylpentanoid scaffold.

Academic Significance and Societal Importance of the Research Achievements

2-(2-フェニルエチル)クロモン類(PECs)の生合成に関与するⅢ型ポリケタイド合成酵素であるPECPSの機能を明らかにしたことで,薬学的に有用なPECsについて代謝工学を利用して大量に合成できる可能性を示しただけでなく,沈香がどのように形成されるかをさらに探求するための知見を得ることで,密栽が行われている沈香の作成に利用される基原植物の生態系を守ることにもつながると期待される。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 Other

All Journal Article (13 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 13 results,  Open Access: 3 results) Remarks (1 results)

  • [Journal Article] Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood2022

    • Author(s)
      Wang Xiao-Hui、Gao Bo-Wen、Nakashima Yu、Mori Takahiro、Zhang Zhong-Xiu、Kodama Takeshi、Lee Yuan-E、Zhang Ze-Kun、Wong Chin-Piow、Liu Qian-Qian、Qi Bo-Wen、Wang Juan、Li Jun、Liu Xiao、Abe Ikuro、Morita Hiroyuki、Tu Peng-Fei、Shi She-Po
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 348-348

    • DOI

      10.1038/s41467-022-27971-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Divergent Synthesis of Decahydroquinoline-Type Poison-Frog Alkaloids2022

    • Author(s)
      Takashima Katsuki、Okada Takuya、Kato Atsushi、Yamasaki Yuhei、Sugouchi Takeshi、Akanuma Shin‐ichi、Kubo Yoshiyuki、Hosoya Ken‐ichi、Morita Hiroyuki、Ito Takuya、Kodama Takeshi、Tanabe Genzoh、Toyooka Naoki
    • Journal Title

      ChemistrySelect

      Volume: 7 Issue: 5

    • DOI

      10.1002/slct.202104533

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemoenzymatic synthesis, computational investigation, and antitumor activity of monocyclic lankacidin derivatives2022

    • Author(s)
      Muslimin Rukman、Nishiura Natsumi、Teshima Aiko、Do Kiep Minh、Kodama Takeshi、Morita Hiroyuki、Lewis Cody Wayne、Chan Gordon、Ayoub Ahmed Taha、Arakawa Kenji
    • Journal Title

      Bioorganic Medicinal Chemistry

      Volume: 53 Pages: 116551-116551

    • DOI

      10.1016/j.bmc.2021.116551

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Shanpanootols G and H, Diterpenoids from the Rhizomes of <i>Kaempferia pulchra</i> Collected in Myanmar and Their Vpr Inhibitory Activities2021

    • Author(s)
      Win NN, Kodama T, Htoo ZP, Hnin SYY, Ngwe H, Abe I, Morita H.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 69 Issue: 9 Pages: 913-917

    • DOI

      10.1248/cpb.c21-00326

    • NAID

      130008081983

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2021-09-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pyrrolactams from Marine Sponge <i>Stylissa massa</i> Collected from Myanmar and Their Anti-Vpr Activities2021

    • Author(s)
      Win Nwet Nwet、Kodama Takeshi、Aye Aung Aung、Lae Khine Zar Wynn、Ngwe Hla、Han Nang Mya、Abe Ikuro、Morita Hiroyuki
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 69 Issue: 7 Pages: 702-705

    • DOI

      10.1248/cpb.c21-00227

    • NAID

      130008060016

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2021-07-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dual Engineering of Olivetolic Acid Cyclase and Tetraketide Synthase to Generate Longer Alkyl-Chain Olivetolic Acid Analogs2021

    • Author(s)
      Lee Yuan-E、Nakashima Yu、Kodama Takeshi、Chen Xinrui、Morita Hiroyuki
    • Journal Title

      Organic Letters

      Volume: 24 Issue: 1 Pages: 410-414

    • DOI

      10.1021/acs.orglett.1c04089

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Total synthesis of decahydroquinoline poison frog alkaloids ent-cis-195a and cis-211a2021

    • Author(s)
      Okada T.、Wu N.、Takashima K.、Ishimura J.、Morita H.、Ito T.、Kodama T.、Yamasaki Y.、Akanuma S.、Kubo Y.、Hosoya K.、Tsuneki H.、Wada T.、Sasaoka T.、Shimizu T.、Sakai H.、Dwoskin L.P.、Hussaini S.R.、Saporito R.A.、Toyooka N.
    • Journal Title

      Molecules

      Volume: 26 Issue: 24 Pages: 7529-7529

    • DOI

      10.3390/molecules26247529

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A New Monoterpene from the Rhizomes of Alpinia galanga and Its Anti‐Vpr Activity2021

    • Author(s)
      Nam Hoang Nhat、Kodama Takeshi、Nwet Win Nwet、Prema、Minh Do Kiep、Abe Ikuro、Morita Hiroyuki
    • Journal Title

      Chemistry & Biodiversity

      Volume: 18 Issue: 10

    • DOI

      10.1002/cbdv.202100401

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new caffeic acid ester and a new ceramide from the roots of Eriosema glomeratum2021

    • Author(s)
      Tabakam Gaetan Tchangou、Kodama Takeshi、Donfack Arno Rusel Nanfack、Nguekeu Yves Martial Mba、Nomin-Erdene Battsengel、Htoo Zin Paing、Do Kiep Minh、Ngouela Silvere Augustin、Tene Mathieu、Morita Hiroyuki、Awouafack Maurice Ducret
    • Journal Title

      Phytochemistry Letters

      Volume: 45 Pages: 82-87

    • DOI

      10.1016/j.phytol.2021.07.019

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-Vpr activities of sesqui- and diterpenoids from the roots and rhizomes of Kaempferia candida2021

    • Author(s)
      Prema、Kodama Takeshi、Nyunt Hnin Htet Wai、Ngwe Hla、Abe Ikuro、Morita Hiroyuki
    • Journal Title

      Journal of Natural Medicines

      Volume: - Issue: 3 Pages: 489-498

    • DOI

      10.1007/s11418-020-01480-z

    • NAID

      40022591517

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan2021

    • Author(s)
      Lee Yuan-E、Kodama Takeshi、Win Nwet Nwet、Ki Dae-Won、Hoang Nhat Nam、Wong Chin Piow、Lae Khine Zar Wynn、Ngwe Hla、Dairi Tohru、Morita Hiroyuki
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 36 Pages: 127787-127787

    • DOI

      10.1016/j.bmcl.2021.127787

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Anti-Vpr activities of homodrimane sesquiterpenoids and labdane diterpenoids from Globba sherwoodiana rhizomes2020

    • Author(s)
      Prema、Kodama Takeshi、Wong Chin Piow、El-Desoky Ahmed H.、Nyunt Hnin Htet Wai、Ngwe Hla、Abe Ikuro、Morita Hiroyuki
    • Journal Title

      Fitoterapia

      Volume: 146 Pages: 104705-104705

    • DOI

      10.1016/j.fitote.2020.104705

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities2020

    • Author(s)
      Ki Dae‐Won、Kodama Takeshi、El‐Desoky Ahmed H.、Wong Chin Piow、Nguyen Hien Minh、Do Kiep Minh、Thai Quang Minh、Ton Nu Lien Huong、Morita Hiroyuki
    • Journal Title

      Chemistry & Biodiversity

      Volume: - Issue: 9 Pages: 2000303-2000303

    • DOI

      10.1002/cbdv.202000303

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Remarks] 富山大学和漢医薬学総合研究所 天然物化学ユニット

    • URL

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

    • Related Report
      2021 Annual Research Report 2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2023-01-30  

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