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Macrocin-O-methyltransferase (TylF) This family consists of bacterial macrocin O-methyltransferase (TylF) proteins. TylF is responsible for the methylation of macrocin to produce tylosin. Tylosin is a macrolide antibiotic used in veterinary medicine to treat infections caused by Gram-positive bacteria and as an animal growth promoter in the swine industry. It is produced by several Streptomyces species. As with other macrolides, the antibiotic activity of tylosin is due to the inhibition of protein biosynthesis by a mechanism that involves the binding of tylosin to the ribosome, preventing the formation of the mRNA-aminoacyl-tRNA-ribosome complex. The structure of one representative sequence from this family, NovP, shows it to be an S-adenosyl-l-methionine-dependent O-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. Specifically, it methylates at 4-OH of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic. It is likely that the key structural features of NovP are common to the rest of the family and include: a helical 'lid' region that gates access to the co-substrate binding pocket and an active centre that contains a 3-Asp putative metal binding site. A further conserved Asp probably acts as the general base that initiates the reaction by de-protonating the 4-OH group of the noviose unit. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",