{Reference Type}: Journal Article {Title}: Nucleoside Phosphorylases make N7-xanthosine. {Author}: Westarp S;Brandt F;Neumair L;Betz C;Dagane A;Kemper S;Jacob CR;Neubauer P;Kurreck A;Kaspar F; {Journal}: Nat Commun {Volume}: 15 {Issue}: 1 {Year}: 2024 Apr 29 {Factor}: 17.694 {DOI}: 10.1038/s41467-024-47287-4 {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.