Rapid hydrolysis rates of thio- and phosphate esters constrain the origin of metabolism to cool, acidic to neutral environments

Creators: Sanden, Sebastian A.^{1, 2}; Butch, Christopher J.^{1, 3}; Bartlett, Stuart^{4, 1}; Virgo, Nathaniel¹; Sekine, Yasuhito^{1, 5, 6}; McGlynn, Shawn Erin^{1, 7, 8}

1. Tokyo Institute of Technology
2. Ruhr University Bochum
3. Nanjing University
4. California Institute of Technology
5. Kanazawa University
6. Tohoku University
7. Blue Marble Space Institute of Science
8. RIKEN Center for Sustainable Resource Science

Abstract

Universal to all life is a reliance on energy carriers such as adenosine triphosphate (ATP) which connect energy-releasing reactions to energy-consuming processes. While ATP is ubiquitously used today, simpler molecules such as thioesters and polyphosphates are hypothesized to be primordial energy carriers. Investigating environmental constraints on the non-enzymatic emergence of metabolism, we find that hydrolysis rates—not hydrolysis energies—differentiate phosphate esters and thioesters. At temperatures consistent with thermophilic microbes, thioesters are favored at acidic pH and phosphate esters at basic pH. Thioacids have a high stability across pH 5–10. The planetary availability of sulfur and phosphate is coincident with these calculations, with phosphate being abundant in alkaline and sulfur in acidic environments. Since both sulfur esters and phosphate esters are uniquely required in metabolism, our results point to a non-thermophilic origin of early metabolism at cool, acidic to neutral environments.

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Acknowledgement

This study was carried out using the TSUBAME 3.0 supercomputer at Tokyo Institute of Technology. S.E.M. acknowledges funding from NSF award no. 1724300 and JSPS KAKENHI grant numbers JP22H01343 and JP22K18278. S.A.S. acknowledges a graduate scholarship received from MEXT of Japan. The authors thank Kuhan Chandru for his assistance on determining the experimental hydrolysis rates. Asset images by brgfx and Freepik on Freepik (www.freepik.com) were used in the generation of the graphical abstract. Contents from this paper were discussed at the "Feasible but Undiscovered Metabolisms: Thermodynamics, Evolution, and the Origin of Life" organized by C. Kempes, C. McShea, and S. McGlynn at the Santa Fe Institute, July 2022.

Code Availability

The MATLAB code used for the combined free energy model, including the experimental parameters for each discussed chemical species, is available as of the date of publication. All original code has been deposited at Zenodo and is publicly available as of the date of publication. https://doi.org/10.5281/zenodo.10801842.

Contributions

S.A.S.: conceptualization, methodology, investigation, visualization, writing – original draft, and writing – review and editing. C.J.B.: methodology, investigation, and writing – review and editing. S.B.: methodology, investigation, and writing – review and editing. N.V.: methodology and writing – review and editing. Y.S.: writing – original draft and writing – review and editing. S.E.M.: conceptualization, supervision, writing – original draft, and writing – review and editing.

Supplemental Material

Document S1. Figure S1 and Tables S1 and S2.
Data S1. Hydrolysis model as MATLAB code, related to Figure 3.

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