Cloning of tlrD, a fourth resistance gene, from the tylosin producer, Streptomyces fradiae.
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.
Zalacain
M
M
Department of Biochemistry, University of Leicester, U.K.
Cundliffe
E
E
D015139:Blotting, Southern; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics; D015870:Gene Expression; D005798:Genes, Bacterial; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D012338:RNA, Ribosomal, 23S / Q000378:metabolism*; D015183:Restriction Mapping; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015645:Tylosin / Q000378:metabolism* / Q000494:pharmacology
D012338:RNA, Ribosomal, 23S; D008780:Methyltransferases; C047346:16S rRNA (adenine(1518)-N(6)-adenine(1519)-N(6))-dimethyltransferase; D015645:Tylosin