Analysis of five tyiosin biosynthetic genes from thetyllBAregion of theStreptomyces fradiaegenome

Abstract

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 0RF2 (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 δTDP-giucose synthase and δTDP-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, δTDP-4-keto, 6-deoxygiucose. ORF5 encodes a thioesterase similar to one encoded in the erythromycin gene cluster of Saccharopolyspora erythraea.