title: Molecular analysis of tlrD, an MLS resistance determinant from the tylosin producer, Streptomyces fradiae.
abstract: The macrolide antibiotic, tylosin (Ty), is produced by Streptomyces fradiae. Two resistance determinants (tlrA, synonym ermSF, and tlrD) conferring resistance to macrolide, lincosamide and streptogramin B type (MLS) antibiotics were previously isolated from this strain, and their products shown to methylate 23S ribosomal RNA (rRNA) at a common site, thereby rendering the ribosomes MLS resistant. However, the TlrA and TlrD proteins differ in their action; the former dimethylates, and the latter monomethylates, the target nucleotide. Here, 2.2 kb of DNA from the tylLM region of the tylosin biosynthetic gene cluster of S. fradiae has been sequenced and shown to encompass tlrD. Comparison of the sequences of tlrA and tlrD (and of their deduced products) with those of related ('erm-type') genes from other actinomycetes suggests that the combined presence of tlrA and tlrD in S. fradiae is not the result of recent gene duplication.
authors.affiliation: Department of Biochemistry, University of Leicester, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Gandecha
authors.forename: E
authors.initials: E
authors.lastname: Cundliffe
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial; D016680:Genome, Bacterial; D055231:Lincosamides; D018942:Macrolides / Q000494:pharmacology; D008780:Methyltransferases / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D015183:Restriction Mapping; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D015645:Tylosin / Q000096:biosynthesis*; D014769:Virginiamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D055231:Lincosamides; D018942:Macrolides; D014769:Virginiamycin; D008780:Methyltransferases; C102927:TlrD protein, Streptomyces fradiae; D015645:Tylosin