Prebiotic formation of thioesters via cyclic anhydrides as a key step in the emergence of metabolism

Thioesters are high-energy derivatives of carboxylic acids that are essential in the functioning of today's living cells. Their central role argues in favor of their early introduction in the abiotic reaction network which led to the emergence of life on Earth. We propose that the first thioesters appeared during the establishment of the reverse tricarboxylic acid (rTCA) cycle, an effective metabolic cycle for the synthesis of organic molecules from CO₂. Most of the acids in this cycle are 1,4-diacids. We show that the formation of a cyclic anhydride from aqueous solutions of succinic or citric acid is possible using drying conditions over silica, as it could happen in an evaporating pond. When these 1,4-diacids are dried in the presence of thiols, thioesters are obtained. Our experimental and theoretical results demonstrate that analogs of succinyl-CoA and citryl-CoA, thioesters from the rTCA cycle, can be produced. Such a process highlights the importance of 1,4-diacids, which would have been introduced in the metabolism then under construction because of their ability to form anhydrides and to be activated in the absence of triphosphates or of any other activating agent. At its beginning, the rTCA cycle should therefore be interpreted mainly as a "1,4-diacid cycle".