Nucleoside Phosphorylases

Abstract

Nucleoside phosphorylases (NPs) are transferases that catalyse the reversible cleavage of the glycosidic bond of ribo-or deoxyribo nucleosides, in the presence of inorganic phosphate, to generate the base and ribose-or deoxyribose-1-phosphate.Since pyrimidine as well as purine nucleoside phosphorylases exist, the combination of both enzymes makes possible the generation of purine nucleosides from pyrimidine ones. As a consequence, NPs from different sources, mainly bacterial, have been exploited as tools for the enzymatic synthesis of nucleoside analogues. These molecules are extensively used as antiviral and anticancer agents because of their ability to act as reverse transcriptase inhibitors or chain terminators in RNA or DNA synthesis.This review covers literature reports from 2000 on, focused mainly on the synthesis of nucleosides by free and immobilised microbial whole cells, along with some examples of modified nucleosides obtained by coupling transglycosylation to other enzymatic reactions.The biological aspects of NPs are also discussed since they became an interesting target for clinical applications due to their key role in nucleotide metabolism. Finally, brief comments about their structures and catalytic mechanisms are included.

One-Pot Multi-Enzymatic Production of Purine Derivatives with Application in Pharmaceutical and Food Industry

“…Modified nucleosides have been traditionally synthesized by different chemical methods, requiring the use of protection-deprotection steps, organic solvents and chemical reagents [4][5][6][7][8][9][10][11]. In this sense, LdNDT has shown to be an interesting sustainable alternative to traditional chemical methods for the synthesis of many different purine nucleosides.…”

“…Covalent immobilization of proteins usually occurs via multipoint attachment through the region with higher density of primary amino groups, especially with ε-NH 2 from lysine residues [22]. Due to this, covalent immobilization techniques usually employ long reaction times (2-24 h) and alkaline conditions (pH [8][9][10]. In this way, the exceptional stability that is displayed by LdNDT and TtHGXPRT [11] under alkaline conditions suggests that they could be efficiently immobilized.…”

“…NAs and NMPs have been traditionally synthesized by chemical methods through multistep processes requiring protection and de-protection steps for the labile groups, and isolation in almost every step due to the poor regio-or stereoselectivity of the reactions [4][5][6][7][8]. These drawbacks lead to a high price of these valuable compounds, limiting their application.…”

“…In this context, the enzymatic synthesis of NAs and NMPs shows many advantages, such as one-pot reactions under mild conditions, high stereo-, and regioselectivity, and an environmentally friendly technology [4][5][6][7][8][9][10][11].…”

“…On the contrary, the salvage pathway is composed by a group of reutilization routes by which the cell can satisfy its purine requirements from endogenous and/or exogenous sources of preformed purines. In this regard, numerous enzymes from purine salvage pathway have become valuable catalysts for mono or multi-enzymatic synthesis of nucleosides and nucleotides, such as nucleoside kinases (NKs) [12][13][14][15], phosphoribosyltransferases [7,[9][10][11], nucleoside phosphorylases [4,8,16,17], 2′-deoxyribosyltransferases [5,[18][19][20], among others.…”