Abstract
Tylosin, a macrolide antibiotic, was co-produced with four structurally similar antibiotics in fermentation cultures of Streptomyces fradiae. Macrocin, desmycosin, lactenocin, and relomycin were found to be components of a common pathway that functions in tylosin biosynthesis. Data obtained by the addition of the purified 14C-labeled antibiotics to cultures of S. fradiae revealed that macrocin and desmycosin were direct precursors of tylosin, whereas lactenocin was an immediate precursor of both macrocin and desmycosin. Incubation of these cultures with [14C]tylosin resulted in an equivalent distribution of radioactive label between relomycin and an unidentified component. The kinetics of incorporation of label into the two species were similar, suggesting that both were derived directly from tylosin. A system that supported that methylation of macrocin to tylosin by cell-free extracts of S. fradiae was developed. A proposed scheme defining the terminal stages of tylosin biosynthesis is presented.
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