title: Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance.
abstract: 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.
authors: Department of Bioactive Molecules, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors: Yasutaka
authors: Y
authors: Hoshino
authors: Shoko
authors: S
authors: Fujii
authors: Hideki
authors: H
authors: Shinonaga
authors: Koshi
authors: K
authors: Arai
authors: Fumiko
authors: F
authors: Saito
authors: Toshio
authors: T
authors: Fukai
authors: Hiroyuki
authors: H
authors: Satoh
authors: Yoshitsugu
authors: Y
authors: Miyazaki
authors: Jun
authors: J
authors: Ishikawa
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006899:Mixed Function Oxygenases; D012293:Rifampin