A prebiotic basis for ATP as the universal energy currency

Abstract

ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

The limits of metabolic heredity in protocells

“…With respect to time scales, these syntheses vary from near instantaneous to days [17][18][19][20]22,23,27,43,33,61,[93][94][95], which is in the right order to sustain an autotrophic protometabolism (as opposed to much longer time scale heterotrophic origins). Temperature requirements are variable, but mostly fall within the standard atmospheric range of 20-100°C [17][18][19][20]22,23,27,33,43,61,[93][94][95], again common in alkaline hydrothermal systems. The exception is fatty acid synthesis [28] which required temperatures of approximately 175°C, but such temperatures are not unusual in higher pressure aqueous systems, or deeper in the crust [98].…”

“…Indeed, we argue that pH gradients are needed to drive flux through protometabolic networks [40,41,95]. The catalysts used are typically period 4 transition metal ions, most prominently iron and copper [16][17][18][19]22,23,25,43,61,93] or their minerals e.g. FeS, Fe x (OH) y and Ni 3 Fe [19,27,94].…”

“…pyridoxal-5-phosphate, but in the absence of enzymatic architecture [93], equivalent to the 'naked cofactors' modelled here. With respect to time scales, these syntheses vary from near instantaneous to days [17][18][19][20]22,23,27,43,33,61,[93][94][95], which is in the right order to sustain an autotrophic protometabolism (as opposed to much longer time scale heterotrophic origins). Temperature requirements are variable, but mostly fall within the standard atmospheric range of 20-100°C [17][18][19][20]22,23,27,33,43,61,[93][94][95], again common in alkaline hydrothermal systems.…”

“…pH can vary, with some syntheses taking place in mildly acidic (approx. 4–5) [ 22 , 23 , 61 ] or neutral pH [ 93 ], and many other syntheses in alkaline (approx. 8–10) conditions [ 19 , 20 , 33 , 43 , 94 ].…”

“…We consider the full network of interactions to evaluate how nucleotide catalysis could contribute to protocell growth. These include nucleotide catalysis of CO 2 fixation and specific protometabolic pathways [34,40,[59][60][61] as well as nucleotide autocatalysis, and the cascade of feedbacks that ensue. The model reveals the necessary architecture of nucleotide catalysis that favours growth and examines whether such processes could generate enough nucleotides to facilitate polymerization and the emergence of genetic heredity.…”