• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Inhibitory mechanism of proline utilization by arginine in Saccharomyces cerevisiae

Research Project

Project/Area Number 21K05504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38060:Applied molecular and cellular biology-related
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Nishimura Akira  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (30781728)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプロリン資化 / 塩基性アミノ酸 / トランセプター / Saccharomyces cerevisiae / アルギニン / 酵母 / トランスセプター / ワイン発酵 / MCC/eisosome
Outline of Research at the Start

酵母Saccharomyces cerevisiaeはワインなどの醸造に用いられ、酵母による原料の資化が酒類の味や風味を決める。プロリンはワインの原料であるブドウ中に最も豊富に含まれるアミノ酸であるが、発酵中の酵母はプロリンをほとんど資化することができず、発酵後も多量に残存する。残存したプロリンは苦味の増加や酸味の減少を引き起こし、最終製品であるワインの酒質を低下させる。申請者は最近、発酵環境中に存在するアルギニンがプロリン資化抑制因子であることを発見した。本研究では、発酵環境下においてプロリンを効率良く資化できる菌株の創製を目的とし、アルギニンによるプロリン資化抑制機構の全容解明を目指す。

Outline of Final Research Achievements

The yeast Saccharomyces cerevisiae hardly assimilates proline during fermentation processes. Our previous studies showed that arginine induces endocytosis of the proline transporter Put4, resulting in inhibition of proline utilization. We first found that two basic amino acids, ornithine and lysine, inhibit proline utilization by inducing Put4 endocytosis in a manner similar to arginine. Our genetic screening revealed that the arginine transporter Can1 is involved in the inhibition of proline utilization. Intriguingly, the arginine uptake activity of Can1 was not required for the arginine-dependent inhibition of proline utilization. More importantly, our biochemical analyses revealed that Can1 activates signaling cascades of protein kinase A in response to extracellular arginine. Hence, we proposed that Can1 regulates proline utilization by functioning as a transceptor possessing the activity of both a transporter and receptor of arginine.

Academic Significance and Societal Importance of the Research Achievements

約30年前から、プロリン資化抑制の解除を目指した研究例は存在するが、いずれの研究もプロリンの資化経路の強化を主眼に置いており、その効果は限定的であった。本研究成果を応用することで、これまでは想像もつかない新規な育種方法の提案が可能となり、プロリン高資化性酵母の構築が可能となる。プロリンが残存しないワインは個性的かつ高品質であることが期待されており、本研究が国内外の醸造業界に与える影響は多大である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (30 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (19 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 19 results,  Open Access: 16 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] UC Davis(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学デービス校(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] カリフォルニア大学デービス校(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality2024

    • Author(s)
      Nishimura Akira、Yoon Sunghyeon、Matsunaga Tetsuro、Ida Tomoaki、Jung Minkyung、Ogata Seiryo、Morita Masanobu、Yoshitake Jun、Unno Yuka、Barayeu Uladzimir、Takata Tsuyoshi、Takagi Hiroshi、Motohashi Hozumi、van der Vliet Albert、Akaike Takaaki
    • Journal Title

      Redox Biology

      Volume: 69 Pages: 103018-103018

    • DOI

      10.1016/j.redox.2023.103018

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional analysis of feedback inhibition-insensitive aspartate kinase identified in a threonine-accumulating mutant of Saccharomyces cerevisiae2024

    • Author(s)
      Isogai Shota、Nishimura Akira、Inoue Akiko、Sonohara Shino、Tsugukuni Takashi、Okada Tomoyuki、Takagi Hiroshi
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 10 Issue: 4

    • DOI

      10.1128/aem.00155-24

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of an arginine transporter in <i>Candida glabrata</i>2023

    • Author(s)
      Nishimura Akira、Tanahashi Ryoya、Nakagami Kazuki、Morioka Yuto、Takagi Hiroshi
    • Journal Title

      The Journal of General and Applied Microbiology

      Volume: 69 Issue: 4 Pages: 229-233

    • DOI

      10.2323/jgam.2023.03.003

    • ISSN
      0022-1260, 1349-8037
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of sulfides and persulfides is not impeded by disruption of three canonical enzymes in sulfur metabolism2023

    • Author(s)
      Zainol Abidin Qamarul Hafiz、Ida Tomoaki、Morita Masanobu、Matsunaga Tetsuro、Nishimura Akira、Jung Minkyung、Hassan Naim、Takata Tsuyoshi、Ishii Isao、Kruger Warren、Wang Rui、Motohashi Hozumi、Tsutsui Masato、Akaike Takaaki
    • Journal Title

      Antioxidants

      Volume: 12 Issue: 4 Pages: 868-868

    • DOI

      10.3390/antiox12040868

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Supersulfide catalysis for nitric oxide and aldehyde metabolism2023

    • Author(s)
      Kasamatsu Shingo、Nishimura Akira、Alam Md. Morshedul、Morita Masanobu、Shimoda Kakeru、Matsunaga Tetsuro、Jung Minkyung、Ogata Seiryo、Barayeu Uladzimir、Ida Tomoaki、Nishida Motohiro、Nishimura Akiyuki、Motohashi Hozumi、Akaike Takaaki
    • Journal Title

      Science Advances

      Volume: 9 Issue: 33 Pages: 1-11

    • DOI

      10.1126/sciadv.adg8631

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PKA-Msn2/4-Shy1 cascade controls inhibition of proline utilization under wine fermentation models2023

    • Author(s)
      Nishimura Akira、Tanahashi Ryoya、Nakazawa Hayate、Oi Tomoki、Mima Misaki、Takagi Hiroshi
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 136 Issue: 6 Pages: 438-442

    • DOI

      10.1016/j.jbiosc.2023.10.005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of Yeast Strains with Higher Proline Uptake and Their Applications to Beer Fermentation2023

    • Author(s)
      Tanahashi Ryoya、Nishimura Akira、Nguyen Minh、Sitepu Irnayuli、Fox Glen、Boundy-Mills Kyria、Takagi Hiroshi
    • Journal Title

      Journal of Fungi

      Volume: 9 Issue: 12 Pages: 1137-1137

    • DOI

      10.3390/jof9121137

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulations and functions of proline utilization in yeast Saccharomyces cerevisiae2023

    • Author(s)
      Nishimura Akira
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 88 Issue: 2 Pages: 131-137

    • DOI

      10.1093/bbb/zbad165

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasmid-free CRISPR/Cas9 genome editing in Saccharomyces cerevisiae2023

    • Author(s)
      Nishimura Akira、Tanahashi Ryoya、Oi Tomoki、Kan Kyoyuki、Takagi Hiroshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 87 Issue: 4 Pages: 458-462

    • DOI

      10.1093/bbb/zbad008

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The arginine transporter Can1 acts as a transceptor for regulation of proline utilization in the yeast Saccharomyces cerevisiae2023

    • Author(s)
      Tanahashi Ryoya、Nishimura Akira、Morita Fumika、Nakazawa Hayate、Taniguchi Atsuki、Ichikawa Kazuki、Nakagami Kazuki、Boundy‐Mills Kyria、Takagi Hiroshi
    • Journal Title

      Yeast

      Volume: - Issue: 8 Pages: 333-348

    • DOI

      10.1002/yea.3836

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improvement of valine and isobutanol production in sake yeast by Ala31Thr substitution in the regulatory subunit of acetohydroxy acid synthase2023

    • Author(s)
      Isogai Shota、Nishimura Akira、Murakami Naoyuki、Hotta Natsuki、Kotaka Atsushi、Toyokawa Yoichi、Ishida Hiroki、Takagi Hiroshi
    • Journal Title

      FEMS Yeast Research

      Volume: 23

    • DOI

      10.1093/femsyr/foad012

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Large-scale screening of yeast strains that can utilize proline2022

    • Author(s)
      Tanahashi Ryoya、Nishimura Akira、Nguyen Minh、Sitepu Irnayuli、Fox Glen、Boundy-Mills Kyria、Takagi Hiroshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 87 Issue: 3 Pages: 358-362

    • DOI

      10.1093/bbb/zbac202

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Arginine inhibits Saccharomyces cerevisiae biofilm formation by inducing endocytosis of the arginine transporter Can12022

    • Author(s)
      Nishimura Akira、Nakagami Kazuki、Kan Kyoyuki、Morita Fumika、Takagi Hiroshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 86 Issue: 9 Pages: 1300-1307

    • DOI

      10.1093/bbb/zbac094

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Cdc25/Ras/cAMP-dependent protein kinase A signaling pathway regulates proline utilization in wine yeast Saccharomyces cerevisiae under a wine fermentation model2022

    • Author(s)
      Nishimura Akira、Ichikawa Kazuki、Nakazawa Hayate、Tanahashi Ryoya、Morita Fumika、Sitepu Irnayuli、Boundy-Mills Kyria、Fox Glen、Takagi Hiroshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 86 Issue: 9 Pages: 1318-1326

    • DOI

      10.1093/bbb/zbac100

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation.2022

    • Author(s)
      Kurane, T., Matsunaga, T., Ida, T., Sawada, K., Nishimura, A., Fukui, M., Umemura, M., Nakayama, M., Ohara, N., Matsumoto, S., Akaike, T., Matsuzaki, G., Takaesu, G.
    • Journal Title

      FASEB Journal

      Volume: 36 Issue: 1

    • DOI

      10.1096/fj.202101074rr

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-Level Production of Isoleucine and Fusel Alcohol by Expression of the Feedback Inhibition-Insensitive Threonine Deaminase in Saccharomyces cerevisiae2022

    • Author(s)
      Isogai Shota、Nishimura Akira、Kotaka Atsushi、Murakami Naoyuki、Hotta Natsuki、Ishida Hiroki、Takagi Hiroshi
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 88 Issue: 5

    • DOI

      10.1128/aem.02130-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longevity regulation by proline oxidation in yeast2021

    • Author(s)
      Akira Nishimura , Yuki Yoshikawa, Kazuki Ichikawa, Tetsuma Takemoto, Ryoya Tanahashi, Hiroshi Takagi
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 8 Pages: 1650-1650

    • DOI

      10.3390/microorganisms9081650

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Gln79 in feedback inhibition of the yeast γ-glutamyl kinase by proline2021

    • Author(s)
      Akira Nishimura, Yurie Takasaki, Shota Isogai, Yoichi Toyokawa, Ryoya Tanahashi, Hiroshi Takagi
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 9 Pages: 1902-1902

    • DOI

      10.3390/microorganisms9091902

    • NAID

      120007175577

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and analysis of a sake yeast mutant with phenylalanine accumulation2021

    • Author(s)
      Nishimura Akira、Isogai Shota、Murakami Naoyuki、Hotta Natsuki、Kotaka Atsushi、Matsumura Kengo、Hata Yoji、Ishida Hiroki、Takagi Hiroshi
    • Journal Title

      Journal of Industrial Microbiology and Biotechnology

      Volume: 49 Issue: 3

    • DOI

      10.1093/jimb/kuab085

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 酵母におけるプロリン資化抑制機構の解明 -プロリンを含まないワイン・ビール製造への挑戦-.2024

    • Author(s)
      西村 明, 高木 博史
    • Organizer
      日本農芸化学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 出芽酵母のアミノ酸代謝による細胞寿命制御2024

    • Author(s)
      西村 明
    • Organizer
      発酵懇話会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] プロリンを含まないワインやビールづくりへの挑戦 -野生酵母コレクションを活用したプロリン資化性酵母の探索-2023

    • Author(s)
      西村 明、棚橋 亮弥、高木 博史
    • Organizer
      農芸化学会2023年度大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] アルギニントランスセプターCan1を介したプロリン資化抑制機構2022

    • Author(s)
      西村 明、高木 博史
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] The arginine transporter Can1 regulates proline uptake as a transceptor in Saccharomyces cerevisiae2022

    • Author(s)
      西村 明、高木 博史
    • Organizer
      若手研究者ネットワーク開拓ワークショップ
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母のプロリン代謝による細胞寿命制御と生理的役割2022

    • Author(s)
      西村 明, 高木博史
    • Organizer
      農芸化学会2022年度大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 母における超硫黄分子の生理的意義-寿命制御と小胞体の恒常性維持-2022

    • Author(s)
      西村明, 高木博史, 赤池孝章
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Research-status Report
  • [Remarks] リサーチマップ

    • URL

      https://researchmap.jp/akira_nishimura/presentations

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi