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Screening of chemical compounds regulating microbial cell growth and metabolism toward bioproduction during stationary phase

Research Project

Project/Area Number 16K14881
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied microbiology
Research InstitutionTokyo Institute of Technology

Principal Investigator

Hirasawa Takashi  東京工業大学, 生命理工学院, 准教授 (20407125)

Research Collaborator WACHI Masaaki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords微生物 / 有用物質生産 / 定常期 / 応用微生物 / 細胞増殖制御 / 代謝制御
Outline of Final Research Achievements

Bioproduction using microorganisms has been conducted by the method coupled with cell growth and that where production of target material(s) has occurred in the absence of cell growth during the stationary phase. Bioproduction during the stationary phase has been realized as one of the effective bioproduction processes in which the resources input, such as carbon and nitrogen sources, can be effectively utilized for only production of the target material(s).
In this study, I have attempted to develop screening system of chemical compounds which can lead cell growth to the stationary phase and maintain metabolic activity in spite of suppressed cell growth toward bioproduction during stationary phase.

Academic Significance and Societal Importance of the Research Achievements

これまで、微生物を用いた定常期における有用物質生産においては、窒素源や金属の枯渇などにより増殖が停止した定常期へと導き、目的物質を生産させる試みがなされてきた。しかしながら、培養の際に常に同じタイミングで窒素源や金属を枯渇させることはむずかしく、再現性よくかつ安価に定常期へと導く新たな技術が必要となる。
本研究は、培養液への化合物の添加のみで微生物細胞を人為的に定常期へと導きかつ有用物質生産を行える新たな技術の開発に向けた研究が展開できるようになると期待される。将来的には、探索した化合物が定常期へと導くメカニズムを明らかにすることができれば、微生物細胞増殖の人為的制御技術の開発にもつながる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (32 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (24 results) (of which Int'l Joint Research: 3 results) Book (3 results)

  • [Journal Article] L-Cysteine production by metabolically engineered Corynebacterium glutamicum2019

    • Author(s)
      Kondoh Mariko、Hirasawa Takashi
    • Journal Title

      Applied Microbiology and Biotechnology

      Volume: 103 Issue: 6 Pages: 2609-2619

    • DOI

      10.1007/s00253-019-09663-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of metabolic engineering targets for improving glycerol assimilation ability of Saccharomyces cerevisiae based on adaptive laboratory evolution and transcriptome analysis2019

    • Author(s)
      Kawai Kazuki、Kanesaki Yu、Yoshikawa Hirofumi、Hirasawa Takashi
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 印刷中 Issue: 2 Pages: 162-169

    • DOI

      10.1016/j.jbiosc.2019.02.001

    • NAID

      40021976360

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth promotion in Corynebacterium glutamicum by overexpression of the NCgl2986 gene encoding a protein homologous to peptidoglycan amidases2019

    • Author(s)
      Mia Fitria Utami, Yoshihiko Matsuda, Noritaka Iwai, Takashi Hirasawa, Masaaki Wachi
    • Journal Title

      Journal of General and Applied Microbiology

      Volume: 印刷中

    • NAID

      130007831595

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium glutamicum during Penicillin-Induced Glutamic Acid Production2018

    • Author(s)
      Hirasawa Takashi、Saito Masaki、Yoshikawa Katsunori、Furusawa Chikara、Shimizu Hiroshi
    • Journal Title

      Biotechnology Journal

      Volume: 13 Issue: 5

    • DOI

      10.1002/biot.201700612

    • Related Report
      2017 Research-status Report
  • [Journal Article] Recent advances in amino acid production by microbial cells2016

    • Author(s)
      Takashi Hirasawa and Hiroshi Shimizu
    • Journal Title

      Current Opinion in Biotechnology

      Volume: 42 Pages: 133-146

    • DOI

      10.1016/j.copbio.2016.04.017

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] コリネ型細菌によるグルタミン酸発酵~メカニズムを理解し応用する2019

    • Author(s)
      平沢 敬
    • Organizer
      日本生物工学会代謝工学研究部会第5回シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 実験室進化によるコリネ型細菌のシステイン耐性株の取得と解析2019

    • Author(s)
      松久和歩、平沢 敬
    • Organizer
      第13回日本ゲノム微生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 銅添加によるコリネ型細菌のグルタミン酸生産誘導2018

    • Author(s)
      平沢 敬
    • Organizer
      平成30年度遺伝研研究会「微生物生態から見えてくる新しい生理機能とその応用」
    • Related Report
      2018 Annual Research Report
  • [Presentation] コリネ型細菌によるグルタミン酸生産におけるビオチン関連因子の関与2018

    • Author(s)
      落合貴子、平沢 敬
    • Organizer
      2018年度グラム陽性菌ゲノム機能会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] Performance of Bacillus subtilis genome-reduced strain for ethanol production host2018

    • Author(s)
      Dita Grinanda、Takashi Hirasawa
    • Organizer
      第17回微生物研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] コリネ型細菌のシステイン生産におけるシスチン取り込みタンパク質ホモログ欠損の効果2017

    • Author(s)
      近藤麻梨子、平沢 敬
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      ウェスティン都ホテル京都・京都女子大学
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] コリネ型細菌によるシステイン発酵生産に向けたシスチン取り込みタンパク質ホモログの探索2017

    • Author(s)
      近藤麻梨子、平沢 敬
    • Organizer
      第11回日本ゲノム微生物学会年会
    • Place of Presentation
      慶應義塾大学湘南藤沢キャンパス
    • Year and Date
      2017-03-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Adaptive laboratory evolution for creating glycerol-assimilating strains of Saccharomyces cerevisiae2017

    • Author(s)
      Takashi Hirasawa, Kazuki Kawai
    • Organizer
      International Union of Microbiological Societies (IUMS2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of disruption of cystine uptake protein homologs on cysteine production in Corynebacterium glutamicum2017

    • Author(s)
      Mariko Kondoh, Takashi Hirasawa
    • Organizer
      International Union of Microbiological Societies (IUMS2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Corynebacterium glutamicumにおける銅(II)添加 によるグルタミン酸生産機構の解明2017

    • Author(s)
      尾形駿介、平沢 敬
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] コリネ型細菌におけるシステイン排出系の探索2017

    • Author(s)
      岸野真弓、近藤麻梨子、松久和歩、平沢 敬
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 長期間の継代培養を基盤とした出芽酵母へのグリセロール資化能の賦与2017

    • Author(s)
      河合一輝、兼崎 友、吉川 博文、平沢 敬
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 長期継代培養によりグリセロール資化能を獲得した出芽酵母の代謝フラックス解析2017

    • Author(s)
      湯澤太路、河合一輝、白井智量、近藤昭彦、平沢 敬
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Bacillus属細菌由来メタノール資化代謝経路の構築と大腸菌への実装2017

    • Author(s)
      矢島宙岳、平沢 敬
    • Organizer
      2017年度グラム陽性菌ゲノム機能会議
    • Related Report
      2017 Research-status Report
  • [Presentation] 実験室進化によるコリネ型細菌のシステイン耐性株の獲得2017

    • Author(s)
      松久和歩、平沢 敬
    • Organizer
      第16回微生物研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] メタノール利用に向けた大腸菌へのメタノール資化代謝経路の導入2017

    • Author(s)
      矢島宙岳、平沢 敬
    • Organizer
      第16回微生物研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 大腸菌によるメタノール資化に向けたBacillus属細菌由来メタノール資化代謝経路の実装2017

    • Author(s)
      矢島宙岳、平沢 敬
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 微生物の代謝工学:人工進化実験を有用宿主創製に活用する2017

    • Author(s)
      平沢 敬
    • Organizer
      平成29年度遺伝研研究会「細菌の構造と代謝の根幹解析研究会~大規模ゲノム交換による微生物育種~」
    • Related Report
      2017 Research-status Report
  • [Presentation] システイン生産に向けたコリネ型細菌の育種とその応用2017

    • Author(s)
      近藤麻梨子、岸野真弓、松久和歩、平沢 敬
    • Organizer
      平成29年度遺伝研研究会「細菌の構造と代謝の根幹解析研究会~大規模ゲノム交換による微生物育種~」
    • Related Report
      2017 Research-status Report
  • [Presentation] Corynebacterium glutamicumによるグルタミン酸生産に対するストレスの影響2016

    • Author(s)
      尾形駿介、齊藤正輝、吉川勝徳、古澤 力、清水 浩、平沢 敬
    • Organizer
      第68回日本生物工学会大会
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2016-09-28
    • Related Report
      2016 Research-status Report
  • [Presentation] コリネ型細菌のシステイン排出に関する因子の同定2016

    • Author(s)
      平沢 敬、岸野真弓
    • Organizer
      2016年度グラム陽性菌ゲノム機能会議
    • Place of Presentation
      KKR ホテル熱海
    • Year and Date
      2016-08-29
    • Related Report
      2016 Research-status Report
  • [Presentation] Metabolic Engineering of Corynebacterium glutamicum for cycteine fermentation2016

    • Author(s)
      Takashi Hirasawa, Mariko Kondoh, Mayumi Kishino
    • Organizer
      Metabolic Engineering 11
    • Place of Presentation
      Awaji Yumebutai International Conference Center
    • Year and Date
      2016-06-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母Saccharomyces cerevisiaeにおける高グリセロール資化能の賦与を目指した実験室進化2016

    • Author(s)
      平沢 敬、河合一輝、兼崎 友、吉川博文
    • Organizer
      東京農業大学生物資源ゲノム解析拠点シンポジウム・研究発表会
    • Place of Presentation
      東京農業大学
    • Related Report
      2016 Research-status Report
  • [Presentation] 実験室進化によりグリセロール資化能を獲得した出芽酵母の代謝フラックス解析2016

    • Author(s)
      湯澤太路、河合一輝、白井智量、近藤昭彦、平沢 敬
    • Organizer
      第15回微生物研究会
    • Place of Presentation
      日本大学湘南キャンパス
    • Related Report
      2016 Research-status Report
  • [Book] Omics-integrated approach for metabolic state analysis of microbial processes. In Applied Bioengineering. Volume 5, Innovations and Future Directions.2017

    • Author(s)
      Hiroshi Shimizu, Chikara Furusawa, Takashi Hirasawa, Katsunori Yoshikawa, Yoshihiro Toya, Tomokazu Shirai, Fumio Matsuda
    • Total Pages
      24
    • Publisher
      Wiley
    • Related Report
      2017 Research-status Report
  • [Book] Industrial Biotechnology: Products and Processes; Glutamic Acid Fermentation: Discovery of Glutamic Acid‐Producing Microorganisms, Analysis of the Production Mechanism, Metabolic Engineering, and Industrial Production Process2016

    • Author(s)
      Takashi Hirasawa, Hiroshi Shimizu
    • Total Pages
      12
    • Publisher
      Wiley‐VCH Verlag GmbH & Co. KGaA
    • Related Report
      2016 Research-status Report
  • [Book] Advances in Biochemical Engineering/Biotechnology; Glutamate Fermentation-2: Mechanism of L-Glutamate Overproduction in Corynebacterium glutamicum2016

    • Author(s)
      Takashi Hirasawa, Masaaki Wachi
    • Total Pages
      16
    • Publisher
      Springer Berlin Heidelberg
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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