ANALYSIS OF 5 TYLOSIN BIOSYNTHETIC GENES FROM THE TYIIBA REGION OF THE STREPTOMYCES-FRADIAE GENOME

The tyllBA region of the tylosin biosynthetic gene cluster of Streptomyces fradiae contains at least five open reading frames (ORFs). ORF1 (tyll) encodes a cytochrome P450 and mutations in this gene affect macrolide ring hydroxylation. The product of ORF2 (tylB) belongs to a widespread family of proteins whose functions are speculative, although tylB mutants are defective in the biosynthesis or addition of mycaminose during tylosin production. ORFs 3 and 4 (tylA1 and tylA2) encode delta TDP-glucose synthase and delta TDP-glucose dehydratase, respectively, enzymes responsible for the first two steps common to the biosynthesis of all three deoxyhexose sugars of tylosin via the common intermediate, delta TDP-4-keto, 6-deoxyglucose. ORF5 encodes a thioesterase similar to one encoded in the erythromycin gene cluster of Saccharopolyspora erythraea.