Acetyl Phosphate as a Primordial Energy Currency at the Origin of Life

Alexandra Whicher,Barry Herschy,Silvana Pinna,Nick Lane,Eloi Camprubi

doi:10.1007/s11084-018-9555-8

Alexandra Whicher, Barry Herschy + Show 3 more

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https://doi.org/10.1007/s11084-018-9555-8

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Abstract

Metabolism is primed through the formation of thioesters via acetyl CoA and the phosphorylation of substrates by ATP. Prebiotic equivalents such as methyl thioacetate and acetyl phosphate have been proposed to catalyse analogous reactions at the origin of life, but their propensity to hydrolyse challenges this view. Here we show that acetyl phosphate (AcP) can be synthesised in water within minutes from thioacetate (but not methyl thioacetate) under ambient conditions. AcP is stable over hours, depending on temperature, pH and cation content, giving it an ideal poise between stability and reactivity. We show that AcP can phosphorylate nucleotide precursors such as ribose to ribose-5-phosphate and adenosine to adenosine monophosphate, at modest (~2%) yield in water, and at a range of pH. AcP can also phosphorylate ADP to ATP in water over several hours at 50 °C. But AcP did not promote polymerization of either glycine or AMP. The amino group of glycine was preferentially acetylated by AcP, especially at alkaline pH, hindering the formation of polypeptides. AMP formed small stacks of up to 7 monomers, but these did not polymerise in the presence of AcP in aqueous solution. We conclude that AcP can phosphorylate biologically meaningful substrates in a manner analogous to ATP, promoting the origins of metabolism, but is unlikely to have driven polymerization of macromolecules such as polypeptides or RNA in free solution. This is consistent with the idea that a period of monomer (cofactor) catalysis preceded the emergence of polymeric enzymes or ribozymes at the origin of life.

Highlights

Phylogenetics and comparative physiology suggest that the earliest cells were autotrophic (Woese 1977; Baross and Hoffman 1985; Morowitz et al 2000; Martin and Russell 2003; Smith and Morowitz 2004; Russell and Martin 2004; Braakman and Smith 2012; Weiss et al 2016), living from relatively unreactive gases such as H2 and CO2, arguably via the acetyl CoA pathway (Russell and Martin 2004; Martin and Russell 2007; Sousa et al 2013; Martin et al 2014; Sojo et al 2016)
We show that acetyl phosphate (AcP) is formed at modest (~2%) yields within minutes under ambient conditions and mild hydrothermal conditions, from the simple 2-carbon precursor thioacetate (Fig. 2)
While most theoretical work has considered methyl thioacetate as a prebiotic equivalent to acetyl CoA, thioacetate has been synthesised from CO and CH3SH under mild hydrothermal conditions (Huber and Wächtershäuser 1997)

Summary

Introduction

Phylogenetics and comparative physiology suggest that the earliest cells were autotrophic (Woese 1977; Baross and Hoffman 1985; Morowitz et al 2000; Martin and Russell 2003; Smith and Morowitz 2004; Russell and Martin 2004; Braakman and Smith 2012; Weiss et al 2016), living from relatively unreactive gases such as H2 and CO2, arguably via the acetyl CoA pathway (Russell and Martin 2004; Martin and Russell 2007; Sousa et al 2013; Martin et al 2014; Sojo et al 2016). From acetyl CoA, a series of analogous hydrogenation and carbonylation reactions can produce carboxylic acids (Krebs cycle intermediates) from pyruvate to isocitrate (Camprubi et al 2017; Muchowska et al 2017). These are the precursors of amino acid, nucleotide, carbohydrate and lipid synthesis in essentially all living cells (Smith and Morowitz 2004, 2016; Martin and Russell 2007). That poses a paradox at the origin of life as the synthesis of monomers such as nucleotides from H2 and CO2 via Krebs cycle intermediates has so far proved intractable under prebiotic conditions, despite its theoretical appeal

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