The mycarose-biosynthetic genes of Streptomyces fradiae, producer of tylosin

The tylCK region of the Streptomyces fradiae genome was sequenced, revealin g an incomplete set of five tyIC genes encoding all-but-one of the enzymes involved in the biosynthesis of mycarose, The latter is a 6-deoxyhexose sug ar required during production of the macrolide antibiotic, tylosin, The mis sing mycarose-biosynthetic gene, tylCVI, was found about 50 kb distant from its functional partners, on the other side of the tylG (polyketide synthas e) gene complex. Mutational analysis, involving targeted gene transplacemen t, was employed to confirm the functions of specific genes, including tylCV I. Particularly interesting was the similarity between the tylosin-biosynth etic mycarosyltransferase enzyme, TylCV, and proteins of the macrolide glyc osyltransferase (MGT) family that inactivate macrolides via glycosylation o f attached sugar residues and are involved in resistance and/or antibiotic efflux. The arrangement of genes within the 'mycarose cluster' would allow their expression as two short operons with divergent, and perhaps co-regula ted. promoters. Whether displacement of tylCVI relative to the other tylC g enes provides additional regulatory opportunities remains to be established .