Bioconversion and Biosynthesis of 16-Membered Macrolide Antibiotics. X. Final Steps in the Biosynthesis of Spiramycin, using Enzyme Inhibitor : Cerulenin

Final steps in the biosynthesis of spiramycin was studied by using cerulenin, a specific inhibitor of fatty acid and polyketide biosynthesis. The spiramycin-related compounds were tested for transformation with Streptomyces ambofaciens, a spiramycin producing strain, under the condition inhibiting the biosynthesis of aglycone by cerulenin. Forocidin I (4'-demycarosyl 9-deforosaminyl-spiramycin I) was converted into forocidin III (3-propionyl forocidin I), neospiramycin I (4'-demycarosyl spiramycin I), neospiramycin III (3-propionyl neospiramycin I), and spiramycin III (3-propionyl spiramycin I). Neospiramycin I was also converted to neospiramycin III and spiramycin III. Spiramycin I was rapidly transformed into spiramycin III, while neospiramycin III was not converted to any other compounds. These results suggested that the binding of forosamine to aglycone precedes the mycaroside formation, and that the acylation of aglycone at C-3 occurs in the final step of spiramycin biosynthesis.