Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance.
We demonstrated that the rox gene of Nocardia farcinica encodes a rifampicin monooxygenase capable of converting rifampicin to a new compound 2'-N-hydroxy-4-oxo-rifampicin with a markedly lowered antibiotic activity. The deletion mutation (Deltarox) of the rox gene gave no significant influence to the rifampicin resistance of N. farcinica. However, transformation with a plasmid containing an overexpressing the rox gene markedly raised the rifampicin resistance in the strain with the deletion mutation of the rpoB2 gene as the principal rifampicin resistance determinant. On the other hand, rifampicin was decolorized by the wild-type strain, whereas it remained intact when incubated with the Deltarox strain. Based on these results, it will be conclusive that the rox gene is capable of initiating rifampicin degradation with a new metabolite formation at the first step and having a role as the secondary rifampicin resistance factor in N. farcinica.
Hoshino
Yasutaka
Y
Department of Bioactive Molecules, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
Fujii
Shoko
S
Shinonaga
Hideki
H
Arai
Koshi
K
Saito
Fumiko
F
Fukai
Toshio
T
Satoh
Hiroyuki
H
Miyazaki
Yoshitsugu
Y
Ishikawa
Jun
J
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D018628:Gene Dosage; D023061:Gene Order; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D009615:Nocardia / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D010957:Plasmids; D012293:Rifampin / Q000378:metabolism* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006899:Mixed Function Oxygenases; D012293:Rifampin