Dragičević Ivan, Barić Danijela, Kovačević Borislav, Golding Bernard T, Smith David M
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb (Croatia); Department of Chemistry, Faculty of Science and Education, University of Mostar, Matice hrvatske bb, 88000 Mostar (Bosnia and Herzegovina).
Chemistry. 2015 Apr 13;21(16):6132-43. doi: 10.1002/chem.201405741. Epub 2015 Mar 6.
Model studies of prebiotic chemistry have revealed compelling routes for the formation of the building blocks of proteins and RNA, but not DNA. Today, deoxynucleotides required for the construction of DNA are produced by reduction of nucleotides catalysed by ribonucleotide reductases, which are radical enzymes. This study considers potential non-enzymatic routes via intermediate radicals for the ancient formation of deoxynucleotides. In this context, several mechanisms for ribonucleotide reduction, in a putative H2 S/HS(.) environment, are characterized using computational chemistry. A bio-inspired mechanistic cycle involving a keto intermediate and HSSH production is found to be potentially viable. An alternative pathway, proceeding through an enol intermediate is found to exhibit similar energetic requirements. Non-cyclical pathways, in which HSS(.) is generated in the final step instead of HS(.) , show a markedly increased thermodynamic driving force (ca. 70 kJ mol(-1) ) and thus warrant serious consideration in the context of the prebiotic ribonucleotide reduction.
益生元化学的模型研究揭示了蛋白质和RNA构建模块形成的令人信服的途径，但DNA的构建模块却并非如此。如今，构建DNA所需的脱氧核苷酸是由核糖核苷酸还原酶催化的核苷酸还原产生的，核糖核苷酸还原酶是一类自由基酶。本研究探讨了通过中间自由基实现脱氧核苷酸古代形成的潜在非酶促途径。在此背景下，利用计算化学对假定的H2S/HS(.)环境中核糖核苷酸还原的几种机制进行了表征。发现一个涉及酮中间体和HSSH生成的受生物启发的机制循环可能是可行的。另一条通过烯醇中间体的途径显示出类似的能量需求。非循环途径，即在最后一步生成HSS(.)而非HS(.)，显示出明显增加的热力学驱动力（约70 kJ mol(-1)），因此在益生元核糖核苷酸还原的背景下值得认真考虑。
