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Cellular membrane engineering of Escherichia coli using membrane lipids from hyperthermophilic archaea

Research Project

Project/Area Number 18K19170
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionNagoya University

Principal Investigator

Hemmi Hisashi  名古屋大学, 生命農学研究科, 准教授 (60302189)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords古細菌 / 古細菌膜脂質 / イソプレノイド / メバロン酸経路 / 細胞膜 / 細胞膜エンジニアリング / 膜エンジニアリング / 大腸菌 / 膜脂質 / 生体膜エンジニアリング / 超好熱性古細菌
Outline of Final Research Achievements

The research was aimed at the establishment of "cell membrane engineering" technology that might enable to change the properties of E. coli membrane by overproducing isoprenoid membrane lipid from a hyperthermophilic archaeon Aeropyrum pernix, which has long hydrocarbon chains. At the same time, we discovered the archaeal mevalonate pathway, which was a novel pathway that supplies biosynthetic precursors for isoprenoid. Thus, we examined the effect of the introduction of the pathway on microbial production of isoprenoid and therefore proved the increase in isoprenoid production when the host was cultivated semi-anaerobically. In addition, we succeeded in synthesizing an unnatural archaeal membrane lipid that has a long hydrocarbon chain by introducing genes from A. pernix and other organisms in combination into E. coli.

Academic Significance and Societal Importance of the Research Achievements

本研究で取り扱った古細菌型メバロン酸経路は、既知のメバロン酸経路と比べ、エネルギー低消費型の代謝経路である。そのため、薬品や工業原料などの有用化合物を多く含むイソプレノイドの微生物生産に同経路を利用することで、宿主から生育に必要なエネルギーを大量に奪うことなく物質生産をさせることが可能になるかもしれない。また、本研究で合成に成功した非天然型古細菌膜脂質は、より厚く安定な細胞膜を構成することが予想される。したがって、大腸菌などの生体膜の性質を変化させて強い微生物を作る「細胞膜エンジニアリング」を今後確立する上で有用なツールとなりうる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (40 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (29 results) (of which Int'l Joint Research: 5 results,  Invited: 7 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of California-Los Angeles(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of California-Los Angeles(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations2021

    • Author(s)
      Okada Miyako、Unno Hideaki、Emi Koh-ichi、Matsumoto Mayuko、Hemmi Hisashi
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Pages: 100679-100679

    • DOI

      10.1016/j.jbc.2021.100679

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 古細菌型メバロン酸経路の発見2021

    • Author(s)
      邊見 久
    • Journal Title

      生化学

      Volume: 93 Pages: 221-224

    • NAID

      40022582932

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Construction of an artificial biosynthetic pathway for hyperextended archaeal membrane lipids in the bacterium Escherichia coli2020

    • Author(s)
      Yoshida Ryo、Hemmi Hisashi
    • Journal Title

      Synthetic Biology

      Volume: 5 Issue: 1

    • DOI

      10.1093/synbio/ysaa018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of the "archaeal" mevalonate pathway from the methanogenic archaeon Methanosarcina mazei in Escherichia coli cells2020

    • Author(s)
      Yoshida Ryo、Yoshimura Tohru、Hemmi Hisashi
    • Journal Title

      Applied Environmental Microbiology

      Volume: 86 Issue: 6

    • DOI

      10.1128/aem.02889-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A heteromeric cis-prenyltransferase is responsible for the biosynthesis of glycosyl carrier lipids in Methanosarcina mazei2019

    • Author(s)
      Emi Koh-ichi、Sompiyachoke Kitty、Okada Miyako、Hemmi Hisashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 2 Pages: 291-296

    • DOI

      10.1016/j.bbrc.2019.09.143

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase by single amino acid mutations2019

    • Author(s)
      Motoyama Kento、Sobue Fumiaki、Kawaide Hiroshi、Yoshimura Tohru、Hemmi Hisashi
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 未定 Issue: 9

    • DOI

      10.1128/aem.00256-19

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans-anhydromevalonate 5-phosphate2018

    • Author(s)
      Hayakawa Hajime、Motoyama Kento、Sobue Fumiaki、Ito Tomokazu、Kawaide Hiroshi、Yoshimura Tohru、Hemmi Hisashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 40 Pages: 10034-10039

    • DOI

      10.1073/pnas.1809154115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 超好熱性アーキア由来ホスホメバロン酸デヒドラターゼの活性中心に存在する鉄硫黄クラスターの解析2021

    • Author(s)
      米山 睦、三野 広幸、保野 陽子、品田 哲郎、吉村 徹、邊見 久
    • Organizer
      2021年度日本農芸化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アーキア型メバロン酸経路の鍵酵素ホスホ-trans-アンヒドロメバロン酸デカルボキシラーゼの酵素学的研究2021

    • Author(s)
      松嶋 夏海、栗木 莉子、保野 陽子、品田 哲郎、吉村 徹、邊見 久
    • Organizer
      2021年度日本農芸化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Methanosarcina mazei 由来プレニル二リン酸特異的 Nudix hydrolase の機能解明2021

    • Author(s)
      石橋 裕美、松嶋 夏海、吉村 徹、邊見 久
    • Organizer
      2021年度日本農芸化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 未培養真正細菌に存在する古細菌型メバロン酸経路2020

    • Author(s)
      邊見 久、Riko Kuriki、吉田 稜
    • Organizer
      第30回イソプレノイド研究会例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アーキア型メバロン酸経路におけるホスホメバロン酸デヒドラターゼの特性評価2020

    • Author(s)
      米山 睦、齋藤甲斐、保野陽子、品田哲郎、吉村 徹、邊見 久
    • Organizer
      2020年度日本農芸化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Does the archaeal mevalonate pathway exist in an unculturable bacterium, Candidatus Promineofilum breve?2020

    • Author(s)
      Riko Kuriki, Ryo Yoshida, Tohru Yoshimura, Hisashi Hemmi
    • Organizer
      2020年度日本農芸化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 古細菌型メバロン酸経路に関与するプレニル化FMN依存性脱炭酸酵素の研究2019

    • Author(s)
      松嶋夏海、吉村 徹、邊見 久
    • Organizer
      日本ビタミン学会第71回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 古細菌に存在する変形メバロン酸経路~その多様性と進化~2019

    • Author(s)
      邊見 久
    • Organizer
      名古屋大学-岐阜大学 微生物系研究室交流会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 古細菌型メバロン酸経路に関与するプレニル化FMN依存性脱炭酸酵素の研究2019

    • Author(s)
      松嶋夏海、品田哲郎、吉村 徹、邊見 久
    • Organizer
      酵素補酵素研究会2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 超好熱アーキアに見出した「第4の」メバロン酸経路2019

    • Author(s)
      邊見 久
    • Organizer
      シンポジウム「好熱菌研究最前線」in微生物ウィーク2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Recounstruction of the archaeal mevalonate pathway from the mesophilic methanogenic archaeon Methanosarcina mazei in Escherichia coli cells2019

    • Author(s)
      Ryo Yoshida, Tohru Yoshimura, Hisashi Hemmi
    • Organizer
      TERPNET 2019 14th International Meeting on the Biosynthesis, Function and Synthetic Biology of Isoprenoids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Discovery of a “fourth” mevalonate pathway from the hyperthermophilic archaeon Aeropyrum pernix2019

    • Author(s)
      Hisashi Hemmi, Hajime Hayakawa, Kento Motoyama, Fumiaki Sobue, Tomokazu Ito, Hiroshi Kawaide, and Tohru Yoshimura
    • Organizer
      Thermophiles 2019 15th International Congress on Thermophiles
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A heteromeric cis-prenyltransferase from the thermophilic archaeon Archaeoglobus fulgidus: purification and biochemical characterization2019

    • Author(s)
      Kitty Sompiyachoke, Koh-ichi Emi, Tohru Yoshimura, Hisashi Hemmi
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 非天然型C25,C30-アーキア膜脂質の生合成経路の構築2019

    • Author(s)
      吉田 稜、吉村 徹、邊見 久
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 超好熱性アーキアAeropyrum pernix由来ホスホメバロン酸デヒドラターゼの解析2019

    • Author(s)
      米山 睦、吉村 徹、邊見 久
    • Organizer
      第29回イソプレノイド研究会例会
    • Related Report
      2019 Research-status Report
  • [Presentation] 超好熱性アーキアAeropyrum pernix由来ホスホ-trans-アンヒドロメバロン酸デカルボキシラーゼの特性評価2019

    • Author(s)
      邊見 久、松嶋夏海、品田哲郎、吉村 徹
    • Organizer
      第20回極限環境生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 「緩い」基質認識が可能にするプレニル基転移反応のリデザイン2019

    • Author(s)
      邊見 久
    • Organizer
      生合成リデザイン第7回公開シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] アーキアに広く保存される「省エネ型」新奇メバロン酸経路を用いた大腸菌でのリコペン生産強化2019

    • Author(s)
      吉田 稜、吉村 徹、邊見 久
    • Organizer
      2019年度日本農芸化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 古細菌型メバロン酸経路の発見2019

    • Author(s)
      邊見 久
    • Organizer
      2019年度日本農芸化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Enhancement of lycopene production in E. coli by introducing the “energy saving” mevalonate pathway conserved in archaea2019

    • Author(s)
      Ryo Yoshida, Tohru Yoshimura, Hisashi Hemmi
    • Organizer
      2019 SAKURA-Bio Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] RIトレーサー実験による古細菌メバロン酸経路の解明2018

    • Author(s)
      邊見 久
    • Organizer
      第42回国立大学ラジオアイソトープ総合センター長会議
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] C25アーキア膜脂質生合成経路の解明と大腸菌における合成2018

    • Author(s)
      吉田 稜, 吉村 徹, 邊見 久
    • Organizer
      日本Archaea研究会第31回講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Picrophilus torridus由来 3,5-ビスホスホメバロン酸デカルボキシラーゼの結晶構造に基づく機能解析2018

    • Author(s)
      青木 瑞希、吉村 徹、邊見 久
    • Organizer
      第28回イソプレノイド研究会例会
    • Related Report
      2018 Research-status Report
  • [Presentation] C25アーキア膜脂質生合成経路の解明と大腸菌における合成2018

    • Author(s)
      吉田 稜, 吉村 徹, 邊見 久
    • Organizer
      2018年度酵素補酵素研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Modification of the substrate specificity of mevalonate 3-kinase from a thermoacidophilic archaeon Thermoplasma acidophilum2018

    • Author(s)
      Kento Motoyama, Tohru Yoshimura, and Hisashi Hemmi
    • Organizer
      Extremophiles 2018: 12th International Congress of Extremophiles
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel modified mevalonate pathway identified from a hyperthemophilic archaeon Aeropyrum pernix2018

    • Author(s)
      Hisashi Hemmi, Hajime Hayakawa, Kento Motoyama, Fumiaki Sobue, Tomokazu Ito, Hiroshi Kawaide, and Tohru Yoshimura
    • Organizer
      Extremophiles 2018: 12th International Congress of Extremophiles
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 幅広い基質特異性を有するcis-プレニルトランスフェラーゼの構造機能研究2018

    • Author(s)
      岡田美弥子、江見 晃一、海野 英昭、吉村 徹、邊見 久
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 超好熱性アーキアから見出された新奇な変形メバロン酸経路2018

    • Author(s)
      邊見 久、早川 祝、本山 賢人、祖父江史明、川出 洋、吉村 徹
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Creation of mevalonate decarboxylase for the production of a second-generation biofuel, isoprenol2018

    • Author(s)
      Hisashi Hemmi
    • Organizer
      ノボザイムズジャパンバイオテクノロジーフォーラム2018
    • Related Report
      2018 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 1.新規メバロン酸経路を有する非古細菌生物2018

    • Inventor(s)
      邊見 久、早川 祝、本山賢人、祖父江史明、吉田 稜
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2022-01-27  

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