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Dynamic control of microbial phenotypes by reprogram of metabolic regulatory network for efficient bioprocess

Research Project

Project/Area Number 18K14065
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionKyushu University

Principal Investigator

Yuki Soma  九州大学, 生体防御医学研究所, 助教 (80781955)

Project Period (FY) 2018-04-01 – 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 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords合成生物学 / 人工遺伝子回路 / 人工代謝経路 / バイオプロセス / クオラムセンシング / 代謝工学 / 進化工学 / 実験室適応進化 / バイオリファイナリー / 代謝フラックス / 微生物代謝 / バイオプロダクション / 代謝アダプテーション / 代謝動態リプログラム
Outline of Final Research Achievements

In bioprocesses, host-intrinsic metabolic pathways and material production pathways are in direct competition with each other, and there is a trade-off between a "phenotype with high bacterial growth potential" and a "phenotype with high material productivity," which is an obstacle to improving productivity in bioprocesses. In this study, we developed a novel metabolic engineering strategy to design and construct microorganisms that can self-regulate their phenotypes optimally according to the progress of bioprocesses. By constructing synthetic genetic circuits that control bacterial growth of Escherichia coli, we succeeded in improving productivity in various useful compounds production. We also constructed an oscillatory circuit based on an artificial synthetic quorum sensing and succeeded in maintaining high productivity continuously in flow-assisted culture.

Academic Significance and Societal Importance of the Research Achievements

化石資源に依存しない持続可能な資源の活用を目指して,微生物などを用いたバイオプロセスによる再生可能資源からの有用物質生産の工業化 (バイオリファイナリー) が注目されている.しかしながら,実用コストを満足する様な十分な生産性を得られていない場合が多く,現状はバイオリファイナリーの実現には至っていない.本研究では,バイオプロセスにおいて普遍的な課題である生産ユニットたる“菌体数”を効率的に確保と生産ユニットあたりの生産効率である“比生産性・比収率”の競合を解消し,生産性の効率化に資する方法論を考案・実証した.本研究は,再生可能資源を原料とした持続可能な有用化合物生産の基盤構築に貢献した.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Quantitative metabolomics for dynamic metabolic engineering using stable isotope labeled internal standards mixture (SILIS).2022

    • Author(s)
      Soma Y#, Takahashi M#, Fujiwara Y, Tomiyasu N, Goto M, Hanai T, Izumi Y, Bamba T*.
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 133(1) Issue: 1 Pages: 46-55

    • DOI

      10.1016/j.jbiosc.2021.09.009

    • NAID

      40022801277

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic metabolic engineering of Escherichia coli improves fermentation for the production of pyruvate and its derivatives2022

    • Author(s)
      Soma Yuki、Yamaji Taiki、Hanai Taizo
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 133 Issue: 1 Pages: 56-63

    • DOI

      10.1016/j.jbiosc.2021.09.015

    • NAID

      40022801279

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calibration-curve-locking database for semi-quantitative metabolomics by gas chromatography/mass spectrometry.2021

    • Author(s)
      Hata K#, Soma Y#, Yamashita T, Takahashi M, Sugitate K, Serino T, Miyagawa H, Suzuki K, Yamada K, Kawamukai T, Shiota T, Izumi Y*, Bamba T*.
    • Journal Title

      Metabolites

      Volume: 11(4) Issue: 4 Pages: 207-207

    • DOI

      10.3390/metabo11040207

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolic alteration of Methylococcus capsulatus str. Bath during a microbial gas-phase reaction.2021

    • Author(s)
      Chen Y-Y#, Soma Y#, Ishikawa M#, Takahashi M, Izumi Y, Bamba T, Hori K*.
    • Journal Title

      Bioresour. Technol.

      Volume: 330 Pages: 125002-125002

    • DOI

      10.1016/j.biortech.2021.125002

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design of synthetic quorum sensing achieving induction timing-independent signal stabilization for dynamic metabolic engineering of E. coli.2021

    • Author(s)
      Soma Y, Takahashi M, Fujiwara Y, Shinohara T, Izumi Y, Hanai T*, Bamba T*.
    • Journal Title

      ACS Synth. Biol.

      Volume: 10(6) Issue: 6 Pages: 1384-1393

    • DOI

      10.1021/acssynbio.1c00008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of acetyl-CoA flux for photosynthetic chemical production by pyruvate dehydrogenase complex overexpression in Synechococcus elongatus PCC 7942.2020

    • Author(s)
      Hirokawa, Y., Kubo, T. (co-first author), Soma, Y., Saruta, F., Hanai, T.
    • Journal Title

      Metab. Eng.

      Volume: 57 Pages: 23-30

    • DOI

      10.1016/j.ymben.2019.07.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production.2019

    • Author(s)
      Honjo, H., Iwasaki, K. (co-first author), Soma, Y., Tsuruno, K., Hamada, H., Hanai, T.
    • Journal Title

      Metab. Eng.

      Volume: 55 Pages: 268-275

    • DOI

      10.1016/j.ymben.2019.08.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 油糧糸状菌 Mortierella alpina の分子育種による遊離脂肪酸生産株のリピドーム解析2020

    • Author(s)
      島田 良美1,下平 武彦2,相馬 悠希2,和泉 自泰2,安藤 晃規1,岸野 重信1,阪本 鷹行3,馬場 健史2,小川 順1,櫻谷 英治3
    • Organizer
      日本農芸化学会 2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 異なる人工遺伝子回路持つ二つの大腸菌による共培養系の構築2019

    • Author(s)
      岩崎 建史朗1,本庄 宏1,相馬 悠希2,鶴野 圭悟1,盧 鎮栄1,濱田 浩幸1,花井 泰三1
    • Organizer
      第71回 日本生物工学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 次世代定量メタボローム解析に資する安定同位体標識内部標準品群調製法の開発2019

    • Author(s)
      相馬 悠希1,2 ,藤原 由梨2,高橋 政友1,後藤 麻衣子1,下平 武彦1,池田 明夏里3,寺内 勉3,和泉 自泰1,2,馬場 健史1,2
    • Organizer
      第71回 日本生物工学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 代謝動態制御を介して菌体集団規模を制御するQuorum Sensing型遺伝子回路の構築とメタボローム解析による機能評価2018

    • Author(s)
      相馬 悠希,篠原 玉樹,藤原 由梨,角田 一真,秦 康祐, 和泉 自泰,花井 泰三,馬場 健史
    • Organizer
      第70回日本生物工学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 絶対定量メタボローム解析の実用化に向けた安定同位体内部標準群のバイオプロダクション2018

    • Author(s)
      藤原由梨,相馬悠希,高橋政友,和泉自泰,馬場健史
    • Organizer
      第25回日本生物工学会 九州支部鹿児島大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Dynamic metabolic engineering harnessing synthetic biological tools and metabolomic analysis2018

    • Author(s)
      Yuki Soma, Yuri Fujiwara, Kohsuke Hata, Yoshihiro Izumi, Takeshi Bamba, Taizo Hanai.
    • Organizer
      Metabolic Engineering 12
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Design of Microbial Cell Factories with Dynamic Gene Regulation2018

    • Author(s)
      Yuki Soma
    • Organizer
      The Asian Synthetic Biology Association (ASBA 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] Google Scholar

    • URL

      https://scholar.google.com/citations?user=tqoJYggAAAAJ&hl=en

    • Related Report
      2020 Research-status Report
  • [Remarks] 研究者プロファイリングツール 九州大学Pure

    • URL

      https://kyushu-u.pure.elsevier.com/ja/persons/yuki-soma

    • Related Report
      2020 Research-status Report
  • [Remarks] 個人HP

    • URL

      https://y-soma.wixsite.com/home

    • Related Report
      2020 Research-status Report
  • [Remarks]

    • URL

      https://y-soma.wixsite.com/home

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 質量分析用標識組成物,代謝物の定量分析法,及び代謝物の動態解析法2019

    • Inventor(s)
      脇村明夏里,寺内勉,馬場健史,和泉自泰,相馬悠希
    • Industrial Property Rights Holder
      脇村明夏里,寺内勉,馬場健史,和泉自泰,相馬悠希
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-090121
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 標識代謝物の製造方法、代謝物の定量方法、及び標識代謝物製造キット2018

    • Inventor(s)
      寺内 勉,脇村 明夏里,馬場 健史,和泉 自泰,相馬 悠希
    • Industrial Property Rights Holder
      寺内 勉,脇村 明夏里,馬場 健史,和泉 自泰,相馬 悠希
    • Industrial Property Rights Type
      特許
    • Patent Publication Number
      2019-024326
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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