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Development of efficient culture process of paclitaxel with low productivity

Research Project

Project/Area Number 20K05240
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionSojo University

Principal Investigator

YamamotoYamamoto Shinjiro  崇城大学, 生物生命学部, 教授 (40262307)

Co-Investigator(Kenkyū-buntansha) 宮坂 均  崇城大学, 生物生命学部, 教授 (60451283)
林 修平  崇城大学, 生物生命学部, 准教授 (30389522)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords植物細胞培養 / 二相培養系 / パクリタキセル / 疎水性イオン液体 / 疎水性媒体 / 細胞培養 / タキサン類 / ポリテトラフルオロエチレン / ポリプロピレン / 二相系培養 / イオン液体 / 疎水性固体 / 二祖系培養 / ストレス
Outline of Research at the Start

高価な抗がん剤パクリタキセル(Paclitaxel;PTX)の安価な生産法として植物細胞培養法が注目されているが、PTXの低生産性と生産物阻害が問題点であった。本研究では、疎水性のイオン液体や固体を利用する二相系の培養条件ならびに細胞活性を促進する物質やPTXなどの二次代謝産物の合成を促進するエリシターを検討して、PTXの生産量を向上させる条件を見出し、高効率にPTXを培養生産するプロセスの開発を目指す。

Outline of Final Research Achievements

Based on our previously obtained data that paclitaxel(PTX) biosynthesis was improved by two-phase culture system using hydrophobic ionic liquids, experiments were conducted to increase the amount of ionic liquid added, and cell growth and PTX production were successfully increased. In addition, PTX productivity could be increased by replacing the ionic liquid with a fresh one in the culture, and the productivity of taxanes containing PTX precursors could also be improved. A two-phase culture system using hydrophobic solids as an alternative medium to ionic liquids was also performed, where polytetrafluoroethylene and polypropylene effectively adsorbed paclitaxel, and polypropylene enhanced PTX productivity. A new culture process utilizing hydrophobic media was proposed.

Academic Significance and Societal Importance of the Research Achievements

本研究は、安全で高効率なパクリタキセルの培養生産プロセスの開発を目指した。疎水性媒体を利用する二相培養系を構築することによって、フィードバック阻害を持つパクリタキセルを疎水性媒体に移動させ、パクリタキセルを効果的に生産させることができた。さらに、疎水性イオン液体を適度な頻度で交換することによってパクリタキセルを飛躍的に培養生産でき、工業的生産の可能性も示唆された。疎水性媒体を利用する二相培養系のバイオプロセスの構築によって高価なパクリタキセルを安価に生産できる可能性も見出されたことから、本研究で得られた研究成果は社会的意義が大きいと考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Effective Production of Paclitaxel and the Related Taxanes in a Plant Cell Culture by<i> in situ</i> Extraction with Sequential Refreshment of Water-Immiscible 1-Butyl-1- methylpyrrolidinium Bis(trifluoromethanesulfonyl)imide2023

    • Author(s)
      Daiki NAGATA, Waka NISHIKAWA, Yuka IZAKI, Shinjiro YAMAMOTO, Shuhei HAYASHI, and Hitoshi MIYASAKA
    • Journal Title

      Solvent Extraction Research and Development, Japan

      Volume: 30 Issue: 2 Pages: 169-175

    • DOI

      10.15261/serdj.30.169

    • ISSN
      1341-7215, 2188-4765
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of Paclitaxel in a Plant Cell Culture by<i> In Situ</i> Extraction with Sequential Refreshment of Water-Immiscible 1-Butyl-1-methylpyrrolidinium Bis(trifluoromethanesulfonyl)imide2022

    • Author(s)
      YAMAMOTO Shinjiro、MURAKAMI Yurina、HAYASHI Shuhei、MIYASAKA Hitoshi
    • Journal Title

      Solvent Extraction Research and Development, Japan

      Volume: 29 Issue: 2 Pages: 73-78

    • DOI

      10.15261/serdj.29.73

    • ISSN
      1341-7215, 2188-4765
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of Paclitaxel Production in Plant Cell Culture Including Increased Amount of Water-immiscible 1-Butyl-1-methylpyrrolidinium Bis(trifluoromethanesulfonyl)imide2021

    • Author(s)
      Shinjiro YAMAMOTO* Yumi KAMIKUBO, Hiroki TANOUE, Michinari IWASAKI, Shuhei HAYASHI, and Hitoshi MIYASAKA
    • Journal Title

      Solvent Extraction Research and Development, Japan

      Volume: 28 Issue: 1 Pages: 109-114

    • DOI

      10.15261/serdj.28.109

    • NAID

      130008049534

    • ISSN
      1341-7215, 2188-4765
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 疎水性イオン液体-培地二相系による植物培養細胞のタキサン類生産の効率化2022

    • Author(s)
      永田大樹、西川和伽、井崎悠華、山本進二郎、林修平、宮坂均
    • Organizer
      化学工学会第53回秋季大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 疎水性イオン液体の交換を伴う二相系培養におけるタキサン類生産の効率化2022

    • Author(s)
      永田大樹、西川和伽、井崎悠華、山本進二郎、林修平、宮坂均
    • Organizer
      第41回溶媒抽出討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] イチイ培養細胞による抗がん剤生産に対する光合成細菌エキスの添加効果2022

    • Author(s)
      西川和伽、永田大樹、井﨑悠華、山本進二郎、林修平、宮坂均
    • Organizer
      第28回日本生物工学会九州支部佐賀大会
    • Related Report
      2022 Annual Research Report
  • [Remarks]

    • URL

      http://www.life.sojo-u.ac.jp/cell/miyasaka/

    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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