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

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.