Diversidade estrutural e evolução da terceira e sexta etapas da biossíntese de purinas em procariotos

Abstract

The biosynthetic purines pathway produces inosine monophosphate in a series of 10 enzymatic reactions. This nucleotide is a precursor of nucleic acids and other molecules of biological importance. In the third step of the purine pathway the compound GAR (Glycinamide ribonucleotide) is converted into FGAR (N-Formylglycinamide ribonucleotide). This reaction can be carried out by two enzymes, PurN or PurT, which use different mechanisms and substrates. In the sixth step of the purine biosynthetic pathway, the compound AIR (Aminoimidazole ribonucleotide) is converted into CAIR (Carboxyaminoimidazole ribonucleotide), by two distinct mechanisms. In prokaryotes, plants and fungi two enzymes, PurK and PurE I, make the conversion of AIR to CAIR using ATP and HCO3 - as substrates. The same reaction can be performed by PurE II that uses CO2 as a substrate. This reaction is described in literature only for animals. The existence of two reaction mechanisms in the third and sixth steps of the purines biosynthetic pathway brings attention to issues about the evolution of these steps as well as the original distribution of these genes in prokaryotic lineages. The results of the present work showed that purN is more distributed than purT on the sampled phyla and classes. The distribution found for purT may be a result of the intense horizontal transfer. Comparative genomics has shown that there are species with purE and purK genes, while others have only purE. The purK phylogeny shows the formation of two major clades. In one of the clades genes are arranged in the order purE/purK, while in the other predominates the order purK/purE. Phylogenetic analysis showed that purE in the organisms that do not have purK form a clade containing purEs from Archaea, Gram positive bacteria, Gram negative and purE II functionally characterized. The data from this work provide a new perspective in understanding the sixth step of the purines biosynthetic pathway, as they indicate that purE II is more widespread in prokaryotes than previously reported in the literature, what can lead to the conclusion that the organism’s way of life may have determined the kind of reaction occurring in the sixth step of the purines biosynthesis.