Cloning of tlrD, a fourth resistance gene, from the tylosin producer, Streptomyces fradiae

Gene. 1991 Jan 2;97(1):137-42. doi: 10.1016/0378-1119(91)90021-3.


In addition to tlrA, tlrB and tlrC, which were previously cloned by others, a fourth antibiotic-resistance gene (tlrD) has been isolated from Streptomyces fradiae, a producer of tylosin (Ty), and cloned in Streptomyces lividans. Like tlrA, tlrD encodes an enzyme that methylates the N6-amino group of the A2058 nucleoside within 23S ribosomal RNA. However, whereas the tlrA protein dimethylates that nucleoside, the tlrD product generates N6-monomethyladenosine. The genes also differ in their mode of expression: tlrA is inducible, whereas tlrD is apparently expressed constitutively, and it has been confirmed that the tlrA-encoded enzyme can add a second methyl group to 23S rRNA that has already been monomethylated by the tlrD-encoded enzyme. Presumably, that is what happens in S. fradiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • Cloning, Molecular
  • Drug Resistance, Microbial / genetics
  • Gene Expression
  • Genes, Bacterial
  • Methylation
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • RNA, Ribosomal, 23S / metabolism*
  • Restriction Mapping
  • Streptomyces / drug effects
  • Streptomyces / genetics*
  • Streptomyces / metabolism
  • Tylosin / metabolism*
  • Tylosin / pharmacology


  • RNA, Ribosomal, 23S
  • Methyltransferases
  • 16S rRNA (adenine(1518)-N(6)-adenine(1519)-N(6))-dimethyltransferase
  • Tylosin