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Investigating natural product biosynthetic pathways in the microbiomes associated with long-lived aquatic vertebrates

Research Project

Project/Area Number 21K06612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionHokkaido University

Principal Investigator

Uria Agustinus Robert  北海道大学, 薬学研究院, 助教 (40889565)

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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordslong-lived animals / chitons / potential bacteria / metagenome / metagenomic analyses / sponge-derived compounds / Saccharomyces cerevisiae / proteasome activity / beneficial microbiomes / microbiomes / aquatic animals / biosynhetic genes / Bacterial cultivation / aquatic vertebrates / cultivation / biosynthesis / 3-D cultivation
Outline of Research at the Start

The important role of gut microbiomes in the prolonged lifespan of eukaryotic hosts has recently been recognized. Our proposed research aims to identify key bacteria, metabolites/natural products, and biosynthetic genes responsible for longevity and healthy lifespan in long-lived aquatic vertebrates. We believe that this has great scientific prospect, because natural products with anti-ageing properties can be developed as pharmaceutical agents that slow ageing or treat age-related diseases, thereby contributing to human healthy lifespan.

Outline of Final Research Achievements

To identify key bacteria, metabolites and biosynthetic genes that may contribute to the longevity of aquatic animals, we initially obtained bacterial isolates from long-lived animals, such as chitons (lifespan ~40 years). We isolated ~430 bacterial strains from different parts of individual chitons. Strains showing resistance to certain antibiotics were subjected to PCR-cloning to detect those with biosynthetic potential. Subsequent metagenomic analyses led to the identification of biosynthetically promising bacteria in two of six studied chiton samples. This is in collaboration with Piel Lab (ETH Zurich) to complement their work on bacterial chemistry (Chem 2023, 9, 12: 3696-713). Using known sponge-derived compounds, we optimized the screening protocol for testing the ability of such compounds to stimulate lifespan in the organism model Saccharomyces cerevisiae. This was based on monitoring proteasome activity of compound-treated yeast lysates.

Academic Significance and Societal Importance of the Research Achievements

Through metagenomic analyses, we identified biosynthetically promising chiton-associated acidobacteria with the ability to produce bioactive sponge-type natural products. This could be a basis for exploring the biosynthetic potential of acidobacterial members from diverse environmental types.

Report

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

    (8 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 4 results)

  • [Int'l Joint Research] ETH Zurich(スイス)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Animal-associated marine Acidobacteria with a rich natural-product repertoire2023

    • Author(s)
      Leopold-Messer Stefan、Chepkirui Clara、Mabesoone Mathijs F.J.、Meyer Joshua、Paoli Lucas、Sunagawa Shinichi、Uria Agustinus R.、Wakimoto Toshiyuki、Piel Joern
    • Journal Title

      Chem (Cell Press journal)

      Volume: 9 Issue: 12 Pages: 3696-3713

    • DOI

      10.1016/j.chempr.2023.11.003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] New Theonellapeptolides from Indonesian Marine Sponge Theonella swinhoei as Anti-Austerity Agents2022

    • Author(s)
      Haedar Jabal Rahmat、Uria Agustinus Robert、Lallo Subehan、Dibwe Dya Fita、Wakimoto Toshiyuki
    • Journal Title

      Marine Drugs (MDPI)

      Volume: 20 Issue: 11 Pages: 661-661

    • DOI

      10.3390/md20110661

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ascidian-associated photosymbionts originated from Manado, Indonesia: Secondary metabolite identification, bioactivity simulation, and biosynthetic insight2021

    • Author(s)
      Rumengan Inneke F.M.、 Roring Vera I.Y.、Haedar Jabal R.、 Siby Mayse S.、Luntungan Aldian H.、Kolondam Beivy J.、Uria Agustinus R.、Wakimoto Toshiyuki
    • Journal Title

      Symbiosis

      Volume: - Issue: 1 Pages: 71-82

    • DOI

      10.1007/s13199-021-00766-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Potential of biosynthetic pathways and biocatalysts from marine metagenomes for the smart eco-bioproduction of highly valuable compounds2022

    • Author(s)
      A.R. Uria
    • Organizer
      SemNasHas XII (National Seminar), Faculty of Agriculture, Gadjah Mada University (UGM) 2022/10
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Marine microbial natural products with unusual building blocks: discovery of their biosynthetic machineries as a basis for drug development2021

    • Author(s)
      A.R. Uria, T. Wakimoto
    • Organizer
      11th International Seminar of Indonesian Society for Microbiology: Microbiology contributions to humanity during and post Covid-19 pandemic 2021/11
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Insights into natural product biosynthesis in marine microbiomes2021

    • Author(s)
      A.R. Uria
    • Organizer
      International Virtual Course on Marine Natural Product at ITB Bandung
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Sustainable use of biodiversity for drug discovery: accessing biosynthetic genes in microbial symbionts of marine sponges2021

    • Author(s)
      A.R. Uria
    • Organizer
      2nd Wallacea International Webinar for Biotechnology & Conservation, Sam Ratulangi University
    • Related Report
      2021 Research-status Report
    • Invited

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

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