Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance
Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance
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DOI：
10.1038/ja.2009.116
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Ishikawa, Jun
中科院分区：
文献类型：
--
作者：
Hoshino, Yasutaka;Fujii, Shoko;Ishikawa, Jun
我们证明，诺卡氏菌farcinica的rox基因编码利福平单加氧酶，能够将利福平转化为新化合物2'-N-羟基-4-氧代-利福平，其抗生素活性显著降低。rox基因的缺失突变（Delta rox）对利福平耐药性无明显影响。闹剧然而，用含有过表达rox基因的质粒转化显著提高了具有rpoB2基因缺失突变的菌株中的利福平抗性，rpoB2基因是主要的利福平抗性决定因素。另一方面，利福平被野生型菌株脱色，而与Delta rox菌株孵育时保持完整。基于这些结果，可以得出结论，rox基因能够在第一步启动利福平降解并形成新的代谢产物，并且在N.闹剧The Journal of Antibiotics（2010）63，23 - 28; doi：10.1038/ja.2009.116; 2009年11月27日在线发表
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 (Delta rox) 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 Delta rox 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. The Journal of Antibiotics (2010) 63, 23-28; doi:10.1038/ja.2009.116; published online 27 November 2009