Nucleoside Phosphorylases make N7-xanthosine

Abstract

Modern, highly evolved nucleoside-processing enzymes are known to exhibit perfect regioselectivity over the glycosylation of purine nucleobases at N9. We herein report an exception to this paradigm. Wild-type nucleoside phosphorylases also furnish N7-xanthosine, a “non-native” ribosylation regioisomer of xanthosine. This unusual nucleoside possesses several atypical physicochemical properties such as redshifted absorption spectra, a high equilibrium constant of phosphorolysis and low acidity. Ultimately, the biosynthesis of this previously unknown natural product illustrates how even highly evolved, essential enzymes from primary metabolism are imperfect catalysts.

Nucleoside-processing enzymes exhibit strict regioselectivity for glycosylation of purine nucleobases at N9. Here, the authors report an exception and show that wild type nucleoside phosphorylases also furnish N7-xanthosine, a non-native ribosylation regioisomer of xanthosine.