Origins Center, Department of Earth Sciences, Utrecht University, Utrecht, The Netherlands.
Centre for Life's Origins and Evolution (CLOE), Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
Astrobiology. 2022 Aug;22(8):981-991. doi: 10.1089/ast.2021.0125. Epub 2022 Jul 12.
The formose reaction has been a leading hypothesis for the prebiotic synthesis of sugars such as ribose for many decades but tends to produce complex mixtures of sugars and often tars. Channeling the formose reaction towards the synthesis of biologically useful sugars such as ribose has been a of origins-of-life research. Here, we tested the hypothesis that a simple, prebiotically plausible phosphorylating agent, acetyl phosphate, could direct the formose reaction towards ribose through phosphorylation of intermediates in a manner resembling gluconeogenesis and the pentose phosphate pathway. We did indeed find that addition of acetyl phosphate to a developing formose reaction stabilized pentoses, including ribose, such that after 5 h of reaction about 10-fold more ribose remained compared with control runs. But mechanistic analyses using liquid chromatography-mass spectrometry showed that, far from being directed towards ribose by phosphorylation, the formose reaction was halted by the precipitation of Ca ions as phosphate minerals such as apatite and hydroxyapatite. Adding orthophosphate had the same effect. Phosphorylated sugars were only detected below the limit of quantification when adding acetyl phosphate. Nonetheless, our findings are not strictly negative. The sensitivity of the formose reaction to geochemically reasonable conditions, combined with the apparent stability of ribose under these conditions, serves as a valuable constraint on possible pathways of sugar synthesis at the origin of life.
该formose 反应一直是前体糖如核糖的生物合成的主要假说已有数十年之久，但往往会产生糖和焦油的复杂混合物。将 formose 反应导向生物有用的糖如核糖的合成一直是起源研究的重点。在这里，我们测试了这样一个假设，即一种简单的、具有前体生物合理性的磷酸化试剂，乙酰磷酸，可以通过类似于糖异生和戊糖磷酸途径的方式，通过磷酸化中间体将 formose 反应定向到核糖。我们确实发现，向正在进行的 formose 反应中添加乙酰磷酸可以稳定戊糖，包括核糖，以至于在 5 小时的反应后，与对照运行相比，核糖的残留量增加了约 10 倍。但是，使用液相色谱-质谱分析的机理分析表明，远非通过磷酸化定向到核糖，formose 反应被 Ca 离子沉淀为磷酸盐矿物（如磷灰石和羟磷灰石）所阻止。添加正磷酸盐也有相同的效果。只有在添加乙酰磷酸时，才能检测到低于定量限的磷酸化糖。尽管如此，我们的发现并不是严格的否定。formose 反应对地球化学合理条件的敏感性，以及在这些条件下核糖的明显稳定性，为生命起源时糖合成的可能途径提供了有价值的限制。
