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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.

Nocardithiocin is a novel thiopeptide compound produced by the pathogenic Nocardia pseudobrasiliensis strain IFM 0757. It shows a strong activity against acid-fast bacilli such as the Mycobacterium and Gordonia species. Nocardithiocin was highly active against rifampicin-resistant as well as -sensitive Mycobacterium tuberculosis strains, and most of the resistant strains were inhibited at concentrations ranging from 0.025 to 1.56 microg ml(-1). The structure of the thiopeptide antibiotic containing thiazole, natural and unnatural amino acids was elucidated by MS and NMR spectral analyses.

Transvalencin Z was isolated from a culture broth of Nocardia transvalensis IFM 10065, a clinical isolate from a Japanese patient with actinomycotic mycetoma. The transvalencin Z structure was determined using NMR and mass spectrometric analyses. The structure is similar to a partial structure of siderophores such as mycobactins and nocobactins, but the compound has no cytotoxic activity. Transvalencin Z shows a strong antimicrobial activity against Gram-positive bacteria, but shows no activity against Gram-negative bacteria, fungi and tumor cells.

A new thiazolidine-type antibiotic with zinc in its structure, designated transvalencin A, was isolated from Nocardia sp. IFM 10065, a clinical isolate from a patient with actinomycotic mycetoma. The strain was identified as Nocardia transvalensis based on its morphological, phenotypic and phylogenetic characteristics. Transvalencin A showed antimicrobial activity against fungi such as Trichophyton mentagrophytes and Cryptococcus neoformans. The antibiotic is also active against Gram-positive bacteria such as Micrococcus luteus. We observed higher activity for fungi in an acidic medium than in a neutral medium.