Analysis of five tylosin biosynthetic genes from the tyllBA 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 (tylI) 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.
Merson-Davies
L A
LA
Department of Biochemistry, University of Leicester, UK.
Cundliffe
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D005798:Genes, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics; D006836:Hydro-Lyases / Q000235:genetics; D008359:Mannose-6-Phosphate Isomerase; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000235:genetics; D016366:Open Reading Frames; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013302:Streptomyces / Q000235:genetics*; D015645:Tylosin / Q000096:biosynthesis*
D001426:Bacterial Proteins; D006460:Hemolysin Proteins; C090673:TlyB protein, Brachyspira hyodysenteriae; D009713:Nucleotidyltransferases; C085243:dTDP-D-glucose synthase; D006836:Hydro-Lyases; C022771:dTDPglucose 4,6-dehydratase; D008359:Mannose-6-Phosphate Isomerase; D015645:Tylosin