ADP-ribosylation of guanosine by SCO5461 protein secreted from Streptomyces coelicolor

► ADP-ribosylating toxins mainly target proteins. However, pierisins ADP-ribosylates guanine residues in dsDNA. ► SCO5461 protein, which shares homology with activity domains of MTX and pierisins, targets guanosine and deoxyguanosine. ► We discovered SCO5461 for the first time as an enzyme which modulates nucleosides. ► We discovered a possibly extracellular function of the ADP-ribosylation reaction.