Evolutionary convergence in the biosyntheses of the imidazole moieties of histidine and purines

Abstract

BackgroundThe imidazole group is an ubiquitous chemical motif present in several key types of biomolecules. It is a structural moiety of purines, and plays a central role in biological catalysis as part of the side-chain of histidine, the amino acid most frequently found in the catalytic site of enzymes. Histidine biosynthesis starts with both ATP and the pentose phosphoribosyl pyrophosphate (PRPP), which is also the precursor for the de novo synthesis of purines. These two anabolic pathways are also connected by the imidazole intermediate 5-aminoimidazole-4-carboxamide ribotide (AICAR), which is synthesized in both routes but used only in purine biosynthesis. Rather surprisingly, the imidazole moieties of histidine and purines are synthesized by different, non-homologous enzymes. As discussed here, this phenomenon can be understood as a case of functional molecular convergence.ResultsIn this work, we analyze these polyphyletic processes and argue that the independent origin of the corresponding enzymes is best explained by the differences in the function of each of the molecules to which the imidazole moiety is attached. Since the imidazole present in histidine is a catalytic moiety, its chemical arrangement allows it to act as an acid or a base. On the contrary, the de novo biosynthesis of purines starts with an activated ribose and all the successive intermediates are ribotides, with the key β-glycosidic bondage joining the ribose and the imidazole moiety. This prevents purine ribonucleotides to exhibit any imidazole-dependent catalytic activity, and may have been the critical trait for the evolution of two separate imidazole-synthesizing-enzymes. We also suggest that, in evolutionary terms, the biosynthesis of purines predated that of histidine.ConclusionsAs reviewed here, other biosynthetic routes for imidazole molecules are also found in extant metabolism, including the autocatalytic cyclization that occurs during the formation of creatinine from creatine phosphate, as well as the internal cyclization of the Ala-Ser-Gly motif of some members of the ammonia-lyase and aminomutase families, that lead to the MIO cofactor. The diversity of imidazole-synthesizing pathways highlights the biological significance of this key chemical group, whose biosyntheses evolved independently several times.

Synthesis of RNA Nucleotides in Plausible Prebiotic Conditions from ab Initio Computer Simulations

“…29 Furthermore, PRPP takes also part in histidine and purine biosynthesis and might have played a role in their RNA world-counterpart. 30 Moreover, a previous ab initio study reported by Sponer et al 31 Pictorial representation of nucleotide formation from PRPP and purine/pyrimidine bases: current biological pathway versus putative prebiotic hydrothermal conditions suggested from the present work. Current living forms exploit the enzymatic catalysis of phosphoribosyltransferases.…”

Purine auxotrophy: Possible applications beyond genetic marker

“…The purine synthesis pathway and its regulation are highly conserved in all eukaryotes from fungi to mammals (Agmon et al, ). Most probably, the last common ancestor had a pathway with the same structure that diversified into the now known three eukaryotic domains (Armenta‐Medina, Segovia, & Perez‐Rueda, ; Vázquez‐Salazar, Becerra, & Lazcano, ).…”

“…Most probably, the last common ancestor had a pathway with the same structure that diversified into the now known three eukaryotic domains (Armenta-Medina, Segovia, & Perez-Rueda, 2014;Vázquez-Salazar, Becerra, & Lazcano, 2018).…”

The Role of Gene Elongation in the Evolution of Histidine Biosynthetic Genes

“…Both TrpF and TrpC are homologs to the HisF/HisA pair; although a prebiotic synthesis of tryptophan has been reported, it is likely that this amino acid has occurred later in evolution. Therefore, the HisF/HisA pair is more ancient than the TrpF and TrpC proteins, antiquity that is in agreement with the key catalytic role played by histidine in many extant enzymes [34].…”

“…HisA, like TrpF, catalyzes an Amadori rearrangement, i.e., the irreversible isomerization of an aminoaldose to an aminoketose [33]. The same chemical rearrangement is responsible for the imidazole ring closure by HisF [34]. HisA and HisF share the ability to bind PRFAR (N9-[(59-phosphoribulosyl)-formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide): HisA catalyzes the formation of PRFAR, and HisF catalyzes an ammonia-dependent reaction in which PRFAR is converted to IGP and AICAR.…”