Enzymic nucleotidylylation of lincosaminide antibiotics

Summary Fermentations ofStreptomyces coelicolor are known to convert lincosaminide antibiotics to mixtures of their inactive 3-(5-ribonucleotides). In the present study, lincomycin, clindamycin and pirlimycin were nucleotidylylated and inactivated using crude enzyme preparations ofS. coelicolor. Optimal conversion is known to occur near pH 6 and to require Mg²⁺ and nucleoside 5-triphosphates. In descending order of activity, inosine, adenosine, guanosine, cytidine and uridine 5-triphosphates functioned as cofactors in these nucleotidylylations. In all instances, 90% of maximal conversion occurred within 24 h. When reaction rates were investigated as functions of enzyme protein addition, pirlimycin appeared to be the superior lincosaminide substrate. Antibiotic activities of these inactivation products could be regenerated through the action of phosphodiesterase, EC 3.1.4.1.