Origin of ATP phosphate esters and sulfur thio-esters in early Life
| Project/Area Number |
23K22614
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| Project/Area Number (Other) |
22H01343 (2022-2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2022-2023) |
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| Section | 一般 |
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| Review Section |
Basic Section 17050:Biogeosciences-related
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| Research Institution | Institute of Science Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
掛川 武 東北大学, 理学研究科, 教授 (60250669)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2024: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | enzyme / evolution / thioester / group transfer potential / origin of life / protein / catalysis / ATP / isotope / Enzyme / Isotope / Origin of life / Energy conservation / Evolution / anaerobe / sulfur isotope |
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| Outline of Research at the Start |
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.
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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Report
(2 results)
Research Products
(4 results)
