A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

THE involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics^1,2-a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world³ could have preceded the RNA world⁴. The components of coenzyme A have been shown to be probable prebiotic compounds: β-alanine, pantoyl lactone and cysteamine^5,6 and possibly adenosine^7,8. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, β-alanine and cysteamine at temperatures as low as 40 ^°C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 ^°C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.