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Origin of ATP phosphate esters and sulfur thio-esters in early Life

研究課題

研究課題/領域番号 23K22614
補助金の研究課題番号 22H01343 (2022-2023)
研究種目

基盤研究(B)

配分区分基金 (2024)
補助金 (2022-2023)
応募区分一般
審査区分 小区分17050:地球生命科学関連
研究機関東京工業大学

研究代表者

McGlynn Shawn・E.  東京工業大学, 地球生命研究所, 准教授 (10751084)

研究分担者 掛川 武  東北大学, 理学研究科, 教授 (60250669)
研究期間 (年度) 2022-04-01 – 2025-03-31
研究課題ステータス 交付 (2024年度)
配分額 *注記
17,290千円 (直接経費: 13,300千円、間接経費: 3,990千円)
2024年度: 5,850千円 (直接経費: 4,500千円、間接経費: 1,350千円)
2023年度: 5,460千円 (直接経費: 4,200千円、間接経費: 1,260千円)
2022年度: 5,980千円 (直接経費: 4,600千円、間接経費: 1,380千円)
キーワードenzyme / evolution / thioester / group transfer potential / origin of life / protein / catalysis / ATP / isotope / Enzyme / Isotope / Origin of life / Energy conservation / Evolution / anaerobe / sulfur isotope
研究開始時の研究の概要

ATP (adenosine triphosphate) is used by all known life forms. However, its is problematic for ancient life because of its molecular complexity and phosphate solubility in ancient iron rich oceans. Sulfur containing thio-esters are simple alternatives to ATP, but their use in deep time has not been investigated with a direct biochemical approach. Is sulfur more ancient than phosphate in early life? We will address this question using purified enzymes that can catalyze S and P dependent chemistry to discover the earliest mechanisms of energy conservation.

研究実績の概要

How life developed the capacity to generate reactive compounds needed in various metabolic reactions has remained a mystery. One class of compounds are the thioesters, which may have preceded complex phosphate containing molecules such as ATP during metabolic evolution. In this year we demonstrated the formation of new carbon-sulfur containing compounds using the enzyme GAPDH with bacterial enzyme homologs. Furthermore, we discovered new chemical routes to carbon-sulfur bond formation, which could represent the very basis for the start of the enzyme reactivity. The formation of these carbon-sulfur compounds is of particular importance, because many researchers have considered that C-S compounds such as cysteine are biological "inventions" which only occurred on Earth after the evolutionary development of life. Along with these so called building block compounds, our findings which show a relationship to compounds critical in energy metabolism advances our understanding of early utilization of sulfur compounds by growing metabolisms. In our next steps we will clarify the reaction using isotope analyses and we will also determine evolutionary relationships to the chemical reactions and their isotope effects.

現在までの達成度 (区分)
現在までの達成度 (区分)

1: 当初の計画以上に進展している

理由

We demonstrated a previously unknown enzyme activity. We are now integrating this knowledge with our understandings of early metabolism and the evolution of metabolic networks and the linkages between geochemistry and enzyme catalyzed biochemistry.

今後の研究の推進方策

In our next phase of research, we will thoroughly investigate the evolutionary history of the enzyme and search for traces of ancestral catalytic activities which may be be harbored by the most ancient homologs. Additionally we will incorporate an understanding of sulfur isotopes in our work to link enzyme findings with the sedimentary isotope record of life on Earth.

報告書

(2件)
  • 2023 実績報告書
  • 2022 実績報告書
  • 研究成果

    (4件)

すべて 2024 2023 2022

すべて 雑誌論文 (3件) (うち査読あり 1件、 オープンアクセス 1件) 学会発表 (1件) (うち国際学会 1件、 招待講演 1件)

  • [雑誌論文] Primitive purine biosynthesis connects ancient geochemistry to modern metabolism2024

    • 著者名/発表者名
      Goldford Joshua E.、Smith Harrison B.、Longo Liam M.、Wing Boswell A.、McGlynn Shawn Erin
    • 雑誌名

      Nature Ecology and Evolution

      巻: 1 号: 5 ページ: 1-11

    • DOI

      10.1038/s41559-024-02361-4

    • 関連する報告書
      2023 実績報告書
  • [雑誌論文] Scaling of Protein Function across the Tree of Life2023

    • 著者名/発表者名
      Gondhalekar Riddhi、Kempes Christopher P、McGlynn Shawn Erin
    • 雑誌名

      Genome Biology and Evolution

      巻: 15 号: 12 ページ: 1-18

    • DOI

      10.1093/gbe/evad214

    • 関連する報告書
      2023 実績報告書
  • [雑誌論文] An Evolutionary History of the CoA‐Binding Protein Nat/Ivy2022

    • 著者名/発表者名
      Liam M. Longo, Hayate Hirai, Shawn Erin McGlynn
    • 雑誌名

      Protein Science

      巻: 31 号: 12 ページ: 1-13

    • DOI

      10.1002/pro.4463

    • 関連する報告書
      2022 実績報告書
    • 査読あり / オープンアクセス
  • [学会発表] Single cell anabolic rates measured by the nanoSIMS: Space, population structure, and relationships2023

    • 著者名/発表者名
      Shawn McGlynn
    • 学会等名
      Quantitative Biology
    • 関連する報告書
      2023 実績報告書
    • 国際学会 / 招待講演

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公開日: 2022-04-19   更新日: 2024-12-25  

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