The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Organic compounds incorporating carbon-metal bonds are called organometallic compounds. Jordan, John Ward, Finn Werner and Nick Lane, 4 October 2022, PLOS Biology.įunding: We are grateful to the Biotechnology and Biological Sciences Research Council to NL, FW and JW (BB/V003542/1) and HR (LIDo Doctoral Training Program), to Gates Ventures (formerly bgc3) to NL, and to the Natural Environment Research Council to AH and NL (2236041). Reference: “A prebiotic basis for ATP as the universal energy currency” by Silvana Pinna, Cäcilia Kunz, Aaron Halpern, Stuart A. The fact that this happens best in water under mild, life-compatible conditions is really quite significant for the origin of life.” It was very surprising to discover the reaction is so selective – in the metal ion, phosphate donor, and substrate – with molecules that life still uses. But I also thought that several phosphorylating agents and metal ion catalysts would work, especially those conserved in life. Lead author Silvana Pinna adds, “ATP is so central to metabolism that I thought it might be possible to form it from ADP under prebiotic conditions. Over time, with the emergence of suitable catalysts, ATP could eventually displace AcP as a ubiquitous phosphate donor, and promote the polymerization of amino acids and nucleotides to form RNA, DNA, and proteins.” “Our results suggest that AcP is the most plausible precursor to ATP as a biological phosphorylator,” Lane says, “and that the emergence of ATP as the universal energy currency of the cell was not the result of a ‘frozen accident,’ but arose from the unique interactions of ADP and AcP. ![]() Finally, they showed that none of the other nucleoside diphosphates accepted a phosphate from AcP.Ĭombining these results with molecular-dynamic modeling, the authors propose a mechanistic explanation for the specificity of the ADP/AcP/iron reaction, hypothesizing that the small diameter and high charge density of the iron ion, combined with the conformation of the intermediate formed when the three come together, provide a “just right” geometry that allows AcP’s phosphate to switch partners, forming ATP. Next, they tested a panel of other small organic molecules for their ability to phosphorylate ADP none were as effective as AcP, and only one other (carbamoyl phosphate) had any significant activity at all. Drawing on data and hypotheses about the chemical conditions of the Earth before life arose, they tested the ability of other ions and minerals to catalyze ATP formation in water none were nearly as effective as iron. ![]() The authors explored all these questions in their new study. Molecular dynamic simulation of ADP and acetyl phosphate Credit: Aaron Halpern, UCL ( CC-BY 4.0) AcP has been shown to phosphorylate ADP to ATP in water in the presence of iron ions, but a host of questions remained after that demonstration, including whether other small molecules might work as well, whether AcP is specific for ADP or instead could function just as well with diphosphates of other nucleosides (such as guanosine or cytosine), and whether iron is unique in its ability to catalyze ADP phosphorylation in water. The most likely candidate, Lane and colleagues believed, was the two-carbon compound acetyl phosphate (AcP), which functions today in both bacteria and archaea as a metabolic intermediate. This means that some other compound may have played a central role in the conversion of ADP to ATP at this stage of evolution. While convincing models do allow for prebiotic formation of the ATP skeleton without energy from already-formed ATP, they also indicate that ATP was likely quite scarce. However, building ATP’s complex chemical structure from scratch is energy intensive and requires six separate ATP-driven steps. Cleavage of that phosphate releases energy to power most types of cellular functions. During cellular respiration, energy is captured when a phosphate is added to ADP (adenosine diphosphate) to generate ATP. ![]() ATP is used by all cells as an energy intermediate.
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