Biotechnological and biomedical applications of enzymes involved in the synthesis of nucleosides and nucleotides

Abstract

Nucleic acid derivatives are involved in cell growth and replication, but they are also particularly important as building blocks for RNA and DNA synthesis. In nature, purine and pyrimidine nucleotides are synthesized through two distinct pathways, de novo and salvage pathways, both depending on 5-phospho-α-D-ribose 1-diphosphate (PRPP) as a key element [1,2]. In the de novo pathway, purine and pyrimidine nucleotides are synthesized from simple molecules such as glycine, glutamine, or aspartate. In contrast, the salvage pathway employs scavenged preformed endogenous or exogenous nucleobases to generate the corresponding nucleoside-50 -monophosphates (NMPs) [3]. Both metabolic routes, de novo and salvage pathways, lead to the synthesis of NMPs, which are subsequently phosphorylated to obtain the corresponding nucleoside-50 -di (NDPs) and triphosphates (NTPs). Moreover, all organisms also generate (20 -deoxy)nucleoside-50 -diphosphates (dNDPs) from NDPs [4], which will be converted to 20 -deoxyribonucleotides (dNTPs), as precursors for DNA synthesis. Additionally, nucleotide derivatives are involved in cell signaling (cyclic nucleotides, cNMPs or c-di-NMPs) [5] and a multitude of different biochemical processes, acting as cofactors (NADP+ ) or energy sources (ATP).