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

Abstract

Some of the factors which influence fermentation of progesterone by the non-germinating spores of a local isolate ofF. solani have been studied in an attempt to improve the yield of the pharmaceutically useful product androstadienedione.

The optimum conditions for the spore-mediated fermentation were defined as: a minimum spore concentration of 2×10⁷ spores/ml., active spores can be obtained only if produced in the presence of an inducer, a minimum of 2 mglml of one of several mono, di or polysaccharides, a minimum incubation period of 48 hours, an optimum temperature of 20–30° C, an optimum pH of 6–7.5, an optimum concentration of 0.8–1 .4 mglml of substrate in the fermentation medium and sufficient aeration by agitation. Several other factors were found not to influence the fermentation either qualitatively or quantitatively; these were: the presence of organic or inorganic nitrogen compounds in the fermentation medium; the use of water, saline or phosphate buffer as a vehicle for the fermentation; and storage of the spores at temperatures of 0–4° C for at least 3 months. In addition, exposure of the spores to temperatures of 4–40° C up to one hour does not affect the fermentation but exposure to higher temperatures reduces the activity of the spores.

Deviations from optimum conditions generally slow the rate of the fermentation and result in an increase in the ratio of androstadienedione to 1–dehydrotestololactone apparently by inhibiting the lactonizing enzyme to a higher degree than the side-chain degrading enzyme, and this oberservation can be utilized to direct the transformation process towards the production of the pharmaceutically useful androstadienedione. In addition, it was found that the same batch of active spores can be used in at least 10 successive fermentations without losing its activity.