Bacterial metabolism of anthracycline antibiotics. Steffimycinone and steffimycinol conversions.
Streptomyces nogalater, UC-2783, and Streptomyces peucetius var. caesius, IMRU-3920/UC-5633, catalyze ketonic carbonyl reduction of steffimycinone (1, Scheme 1). Using cell-free preparations of S. nogalater, the process of ketonic carbonyl reduction has been shown to be TPNH linked. The product, steffimycinol (2), is reduced further by Aeromonas hydrophila, 2C/UC-6303, by the process of microaerophilic conversion of anthracyclinones previously reported1,2) with the result being the formation of 7-deoxysteffimycinol (3). The products (2 and 3) were isolated by extraction from the fermentations followed by chromatographic purification. Identification was by comparison of various physical properties and spectral data with those of authentic materials obtained by chemical means. Catalytic activity of the crude enzyme preparations of S. nogalater was lost by dialysis by restored by addition of TPNH although not by addition of DPNH demonstrating TPNH dependence. The reaction rate increased linearly with added crude enzyme protein up to 4 mg/ml and was highest between pH 6.5 and 7.0.
Bacterial metabolism of anthracycline antibiotics. Steffimycinone and steffimycinol conversions. Streptomyces nogalater, UC-2783, and Streptomyces peucetius var. caesius, IMRU-3920/UC-5633, catalyze ketonic carbonyl reduction of steffimycinone (1, Scheme 1). Using cell-free preparations of S. nogalater, the process of ketonic carbonyl reduction has been shown to be TPNH linked. The product, steffimycinol (2), is reduced further by Aeromonas hydrophila, 2C/UC-6303, by the process of microaerophilic conversion of anthracyclinones previously reported1,2) with the result being the formation of 7-deoxysteffimycinol (3). The products (2 and 3) were isolated by extraction from the fermentations followed by chromatographic purification. Identification was by comparison of various physical properties and spectral data with those of authentic materials obtained by chemical means. Catalytic activity of the crude enzyme preparations of S. nogalater was lost by dialysis by restored by addition of TPNH although not by addition of DPNH demonstrating TPNH dependence. The reaction rate increased linearly with added crude enzyme protein up to 4 mg/ml and was highest between pH 6.5 and 7.0.