Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Nat Commun. 2017 May 19;8:15270. doi: 10.1038/ncomms15270.
Understanding prebiotic nucleotide synthesis is a long standing challenge thought to be essential to elucidating the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Here, we tackle this mutual incompatibility by recognizing that the 8-oxo-purines share an underlying generational parity with the pyrimidine nucleotides. We present a divergent synthesis of pyrimidine and 8-oxo-purine nucleotides starting from a common prebiotic precursor that yields the β-ribo-stereochemistry found in the sugar phosphate backbone of biological nucleic acids. The generational relationship between pyrimidine and 8-oxo-purine nucleotides suggests that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids prior to the emergence of the canonical nucleotides of biology.
理解前体核苷酸的合成是一个长期存在的挑战，被认为是阐明地球上生命起源的关键。最近，已经取得了显著的进展，但迄今为止，所有提出的合成方法分别解释了嘧啶和嘌呤核糖核苷酸；没有从共同前体提出分歧的合成。此外，已经证明的嘧啶和嘌呤核苷酸的前体合成在相互不相容的条件下进行。在这里，我们通过认识到 8-氧嘌呤与嘧啶核苷酸具有潜在的代际等价性来解决这种相互不兼容性。我们提出了一种从共同的前体物质出发，对嘧啶和 8-氧嘌呤核苷酸进行分歧合成的方法，得到了生物核酸糖磷酸骨架中发现的β-核糖立体化学。嘧啶和 8-氧嘌呤核苷酸之间的代际关系表明，在生物学的典型核苷酸出现之前，8-氧嘌呤核糖核苷酸可能在原始核酸中发挥了关键作用。
