Systems Chemistry in the Prebiotic Synthesis of RNA

生命起源前 RNA 合成中的系统化学

• 批准号: EP/H044140/1
• 负责人: John Sutherland
• 金额: $ 79.59万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FH044140%2F1
• 关键词: Systems; Chemistry; Prebiotic; Synthesis; RNA

It is though that during the origin of life on Earth there was a phase when the nucleic acid RNA served the dual roles of information storage and catalysis. The 'RNA world hypothesis' is strongly supported by much recent biological work, but until our recent EPSRC funded work, there had been little by way of chemical explanation as to how RNA might have been generated prebiotically on the early Earth. To quote from a New York Times article written about our work earlier this year: 'For more than 20 years researchers have been working on this problem. The building blocks of RNA, known as nucleotides, each consist of a chemical base, a sugar molecule called ribose and a phosphate group. Chemists quickly found plausible natural ways for each of these constituents to form from natural chemicals. But there was no natural way for them all to join together. The spontaneous appearance of such nucleotides on the primitive earth would have been a near miracle, two leading researchers, Gerald Joyce and Leslie Orgel, wrote in 1999. Others were so despairing that they believed some other molecule must have preceded RNA and started looking for a pre-RNA world.The miracle seems now to have been explained. In the article in Nature, Dr. Sutherland and his colleagues Matthew W. Powner and Batrice Gerland report that they have taken the same starting chemicals used by others but have caused them to react in a different order and in different combinations than in previous experiments. they discovered their recipe, which is far from intuitive, after 10 years of working through every possible combination of starting chemicals. Instead of making the starting chemicals form a sugar and a base, they mixed them in a different order, in which the chemicals naturally formed a compound that is half-sugar and half-base. When another half-sugar and half-base are added, the RNA nucleotide called ribocytidine phosphate emerges. A second nucleotide is created if ultraviolet light is shined on the mixture.'So far so good, but quite a bit remains to be done if RNA itself is to be made, and the current proposal seeks funds to finish the job. In particular, we want to:i) find a route to activated purine nucleotides - we think we can do this from a by-product of the pyrimidine nucleotide synthesisii) sort out the chirality issue (certain molecules exist in left and right handed forms, and RNA is a polymer of right handed nucleotides) - we think we can do this using a crystallisation 'trick' followed by a phosphate-catalysed reactioniii) find a route to glyceraldehyde which is a key intermediate in the synthesis, but which is not considered to have been a prebiotic feedstock moleculeiv) optimise conditions for stringing the activated nucleotides together to generate RNA

在地球生命起源的过程中，有一个阶段，核酸RNA扮演着信息存储和催化的双重角色。“RNA世界假说”得到了最近许多生物学工作的有力支持，但直到我们最近的EPSRC资助的工作，几乎没有通过化学解释RNA如何在早期地球上产生。引用今年早些时候《纽约时报》一篇关于我们工作的文章：“20多年来，研究人员一直在研究这个问题。RNA的基本组成部分，即核苷酸，每一个都由一个化学碱基、一个称为核糖的糖分子和一个磷酸基团组成。化学家们很快就找到了这些成分从天然化学物质中形成的合理的自然方法。但是没有自然的方式让他们都结合在一起。两位主要研究人员杰拉尔德·乔伊斯和莱斯利·奥格尔在1999年写道，这种核苷酸在原始地球上的自发出现几乎是一个奇迹。另一些人则非常绝望，他们相信一定有其他分子先于RNA出现，并开始寻找前RNA的世界，这个奇迹现在似乎得到了解释。在《自然》杂志的文章中，萨瑟兰博士和他的同事马修W。Powner和Batrice Gerland报告说，他们采用了与其他人使用的相同的起始化学品，但使它们以不同的顺序和不同的组合反应，而不是以前的实验。他们发现了他们的配方，这是远远不是直观的，经过10年的工作，通过每一个可能的组合开始化学品。他们没有让起始化学物质形成糖和碱，而是以不同的顺序混合它们，其中化学物质自然形成半糖半碱的化合物。当另一个半糖和半碱基被添加时，称为核糖胞苷磷酸的RNA核苷酸出现。如果紫外线照射在混合物上，就会产生第二种核苷酸。“到目前为止一切顺利，但如果要制造RNA本身，还有很多工作要做，目前的提案寻求资金来完成这项工作。特别是，我们想：i）找到一条活化嘌呤核苷酸的途径-我们认为我们可以从嘧啶核苷酸合成的副产物中做到这一点ii）解决手性问题（某些分子以左手和右手形式存在，RNA是右手核苷酸的聚合物）-我们认为我们可以使用结晶“技巧”，然后进行磷酸盐催化反应来做到这一点iii）找到一条甘油醛的途径，甘油醛是合成中的关键中间体，但不被认为是益生元原料分子iv）优化将活化核苷酸串联在一起以产生RNA的条件

项目成果

Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.

• DOI: 10.1038/nchem.1626
• 发表时间: 2013-05
• 期刊: Nature chemistry
• 影响因子: 21.8