MICROBIOLOGICAL TRANSFORMATIONS OF STEROIDS – IV. Factors Affecting the Transformation of Progesterone by Non-germinating Spores of Cylindrocarponradicicola

Abstract

Some of the factors which influence the transformation of progesterone by non-germinating spores of C. radicicola have been studied in an attempt to suppress lactonization and thus improve the yield of the pharmaceutically useful product; androstadienedione.

The transformation was found not to require preinduction of the spores, a source of energy or agitation and could be carried out in distilled water. The pH of the fermentation, the type of buffer, temperature of the fermentation, substrate concentration and metal ions affect the extent of transformation and the ratio of different products.

Total inhibition of lactonization is observed with induced spores in presence of tetracycline while partial inhibition is observed with several substances such as cycloheximide, potassium cyanide, 5–methyl-phenazinuim methosulfate, cobalt nitrate, ferrous sulfate, succinate buffer pH 6, borate buffer pH 10, mannitol or by carrying the reaction at 25° C or using non-induced spores. In some of these cases however, small amounts or traces of new products also accumulate.

Partial inhibition of the over-all transformation together with total inhibition of lactonization is observed with acetate buffer pH S, butyric acid, 8–hydroxyquinoline, 2,6–dichlorophenol indophenol, high substrate concentration, pre-treatment of the spores at 60° C or by carrying the reaction at 4° C. Partial inhibition of the over-all transformation together with more powerfull inhibition of lactonization is observed with phosphate buffer pH 8, Tris buffer pH 6, or α–Keto-glutaric acid.

The entire reaction is arrested with caproic acid, caprylic acid, copper sulfate, mercuric chloride, sodium azide, pre-treatment of the spores at 100° C or using tetracycline or cycloheximide with non-induced spores.

The significance of these findings is discussed.