Microbial O-phosphorylation of macrolide antibiotics.

Crude enzymepreparations of Streptomyces coelicolor (Miiller), UC 5240 in the presence of ATP and Mg2+ catalyzed the conversion of oleandomycin, tylosin, leucomycin A3 and a mixture of spiramycins I, II and III to their antibiotically inactive I'-O-phosphates.10 Under identical conditions, erythromycin was converted to anhydroerythromycin-Z'-O-phosphate.10 As O-phosphorylation of aminocyclitols, lincosaminides and nucleosides is a well-known mechanism of antibiotic inactivation,2) O-phosphorylation of macrolides was investigated as a transformation of potential significance. Such an O-phosphorylating enzyme could protect macrolide producing microorganisms during antibiotic biosynthesis or could be a mechanism of macrolide resistance in pathogens. The data reported here concerns the conversion of oleandomycin and a mixture of spiramycins I, II and III to their 2'-0-phosphates by S. coelicolor in fermentation (Fig. 1). Such an investigation was considered to be an important step in establishing the physiological significance of these <9-phosphorylations. The antibacterial activities of these macrolide-2'-0phosphates were also investigated.