Key steps from the “RNA World” to the “DNA World”

¹ Université de Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, ICMG FR 2607, 470 rue de la Chimie BP 53, F-38041 Grenoble, France
² Present address: Centre d’Ecologie Fonctionnelle et Evolutive CNRS, UMR 5175, 1919 oute de Mende 34293 Montpellier Cedex 5, France
³ Present address: Université Claude Bernard Lyon/CNRS, UMR 5246, Institut de Chimie Biochimie Moléculaires et Supramoléculaires (ICBMS), La Doua, France

Abstract

In the « RNA World » hypothesis of the origin of life, RNAs are assumed to be the central macromolecules able to self-replicate, conserve information and catalyze the reactions necessary for a primitive metabolism and many enzymatic cofactors may be regarded as molecular fossils of the “RNA World”. In the key steps involved in the transition from the RNA World to the DNA World, two main steps can be distinguished: (i) the synthesis of 2’-deoxyribonucleotides from ribonucleotides catalyzed nowadays by the enzyme ribonucleotide reductase and (ii) the synthesis of thymine, a base specific for DNA, from uracil which is a base specific for RNA, catalyzed today by the enzyme thymidylate synthase. In regard to the chemistry of sulfur used by both enzymes for achieving their respective catalysis, we were interested in the search for simple sulfur reactions able to catalyze such transformations and report here on first results in an approach from thionucleosides to the catalysis involved in the conversion of uracil to thymine. In the RNA World, the recruitment of cofactors was crucial to expand the catalytic repertoire of RNA and we also describe interesting preliminary results obtained in the prebiotic synthesis of pyridoxal (vitamin B6) that is the precursor of the key coenzyme pyridoxal phosphate (PLP) able to catalyze nowadays seven different enzymatic reactions.