Biocatalytic Synthesis of Nucleotide Analogues

Significance

Phosphoribosyltransferases (PRTs) are enzymes that mediate the addition of nucleobases to ribose activated as phosphate and/or pyrophosphate. The authors describe the application of such biocatalysts for the synthesis of nucleotide analogues. Directed evolution of wild-type hypoxanthine phosphoribosyltransferase (HPRT) from E. coli provided variant 8B3PRT. This mutant catalyzes the reaction of phosphoribosyl pyrophosphate (PRPP) 1 with various hetero­cycles 2 to the corresponding nucleotide analogues 3 in high yields and complete β-selectivities.