Whicher Alexandra, Camprubi Eloi, Pinna Silvana, Herschy Barry, Lane Nick
Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
Orig Life Evol Biosph. 2018 Jun;48(2):159-179. doi: 10.1007/s11084-018-9555-8. Epub 2018 Mar 3.
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.
新陈代谢通过经由乙酰辅酶A形成硫酯以及ATP对底物的磷酸化作用而启动。有人提出，诸如硫代乙酸甲酯和乙酰磷酸等前生物等效物在生命起源时催化类似反应，但其水解倾向对这一观点提出了挑战。在此，我们表明，在环境条件下，硫代乙酸酯（而非硫代乙酸甲酯）可在数分钟内在水中合成乙酰磷酸（AcP）。根据温度、pH值和阳离子含量，AcP在数小时内保持稳定，使其在稳定性和反应活性之间达到了理想的平衡。我们表明，AcP能够在水中将核苷酸前体（如核糖）磷酸化为5-磷酸核糖，将腺苷磷酸化为单磷酸腺苷，产率适中（约2%），且在一系列pH值条件下均可发生。在50℃下，AcP还能在数小时内将ADP磷酸化为ATP。但AcP并未促进甘氨酸或AMP的聚合。甘氨酸的氨基优先被AcP乙酰化，尤其是在碱性pH值条件下，这阻碍了多肽链的形成。AMP形成了多达7个单体的小聚集体，但在水溶液中，这些聚集体在AcP存在的情况下并未发生聚合。我们得出结论，AcP能够以类似于ATP的方式磷酸化具有生物学意义的底物，促进新陈代谢的起源，但不太可能在自由溶液中驱动多肽或RNA等大分子的聚合。这与生命起源时聚合物酶或核酶出现之前存在一段单体（辅因子）催化时期的观点一致。
