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High protein secretion through artificial enlargement and enforcement of the endoplasmic reticulum in yeast cells

Research Project

Project/Area Number 22K19135
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 InstitutionNara Institute of Science and Technology

Principal Investigator

Kimata Yukio  奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (60263448)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords小胞体 / 酵母 / 小胞体ストレス応答 / 脂質生産 / 分泌タンパク質生産 / オルガネラ / 油脂 / タンパク質分泌 / タンパク質
Outline of Research at the Start

遺伝子組換え酵母による有用分泌蛋白質や脂溶性二次代謝産物の生産は、広範囲に実用化が進められている技術である。しかし、酵母細胞においては、それらの生合成の場である小胞体のサイズは概して小さく、高い収量を得られないことが多い。そこで本研究では、小胞体の表面積や体積が増大した酵母細胞の作出を目指す。本研究ではまず、網羅的遺伝子欠損酵母株ライブラリーのスクリーニングなどを通じ、小胞体の伸展や層畳化に関わる遺伝子を同定し、小胞体拡張のメカニズム解明へと繋げる。そして、得られた知見を活用して人為的かつ恒常的に酵母細胞の小胞体を拡張し、実際に有用分泌蛋白質や脂溶性分子の収量を向上できるかを検証する。

Outline of Final Research Achievements

The endoplasmic reticulum (ER) is an organelle that serves as a site for the biosynthesis of lipids and secretory proteins. Dysfunction of the ER is known as ER stress. In almost all of the eukaryotic cells, the expression of proteins that constitute the ER is induced at the transcriptional level in response to ER stress. This is the ER stress response. In this study, we have developed a method to rescue the growth delay in yeast cells that artificially and constitutively expressed Hac1, a transcription factor that promotes the ER stress response. In such cells, the ER was highly extended even under non-stressed conditions, leading to an increase in the production of lipids and secretory proteins.

Academic Significance and Societal Importance of the Research Achievements

酵母は安価かつ簡便に培養できる単細胞の真核生物であり、他の真核生物の遺伝子を導入することにより、本来は酵母が作らない物質を合成させることが可能となる。例えば、ヒトの遺伝子の導入により、抗体やインターフェロンなどヒト由来タンパク質を分泌生産させ、それらは医薬品として用いることができる。また、テルペノイドなど植物が作る脂質類を酵母に作らせる技術も開発されている。これらの有用物質は細胞の中で小胞体と呼ばれる部位で合成されており、本研究では、酵母の遺伝子操作にて、小胞体を伸展し、有用物質の産生量を向上することに成功した。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (6 results)

All 2023 2022

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in Pichia pastoris cells independent of HAC12023

    • Author(s)
      Fauzee Yasmin Nabilah Binti Mohd、Yoshida Yuki、Kimata Yukio
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 1157146-1157146

    • DOI

      10.3389/fmicb.2023.1157146

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An ER-accumulated mutant of yeast Pma1 causes membrane-related stress to induce the unfolded protein response2023

    • Author(s)
      Phuong Huong Thi、Ishiwata-Kimata Yuki、Kimata Yukio
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 667 Pages: 58-63

    • DOI

      10.1016/j.bbrc.2023.05.044

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fast-Growing Saccharomyces cerevisiae Cells with a Constitutive Unfolded Protein Response and Their Potential for Lipidic Molecule Production2022

    • Author(s)
      Nguyen Phuong Thi Mai、Ishiwata-Kimata Yuki、Kimata Yukio
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 88 Issue: 21

    • DOI

      10.1128/aem.01083-22

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] Artificial Organelle Enlargement toward Generation of Industrially Valuable Yeast Strains2023

    • Author(s)
      Yukio Kimata
    • Organizer
      The 6th Rencontres de Quy Nhon: International Biology Conference 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tet-Offシステムを用いたUPRの人為的制御とその応用2023

    • Author(s)
      門口将己、木俣行雄
    • Organizer
      酵母遺伝学フォーラム第56回研究報告会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 恒常的UPR活性型酵母の性状と応用2022

    • Author(s)
      木俣行雄
    • Organizer
      小胞体ストレス研究会
    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2025-01-30  

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