” Pseudo-Crystallofermentation “of Steroid: A New Process for Preparing Prednisolone by a Microorganism

Abstract

The discovery of remarkable therapeutic properties of prednisone, prednisolone and related compounds has stimulated wide interest in finding simpler and more economical methods of preparing such 1-dehydro hormones. A large number of microorganisms were tested for their ability to carry out 1-dehydrogenation of steroids and some of them were found able to do so (1). However, paradoxically, these processes are also adversely affected by the generic characteristics of microorganisms and the steroids. Namely, the former grow well in an aqueous medium, while the latter are generally insoluble in water. Thus, the steroidal fermentations were previously carried out by the addition of a water-miscible organic solvent such as a lower aliphatic alcohol or ketone which affected harmfully to microorganisms. Accordingly, the addition of the steroid to the culture broth of microorganism was naturally limited by the concentration of the organic solvent employed. In the fermentation of steroid by the method as mentioned above, for all practical purposes, the maximum concentration of the substrate was about 0.1 per cent, i.e., 1 g steroid per 1 litre of the broth-solution. Therefore, large fermenters, extracters and other related apparatus were necessary for the microbial production of the 1-dehydro steroids on an industrial scale. In addition, a considerable amount of the steroid was taken to form overoxidation products in some cases of the fermentation. To overcome these defects, attempts have been made to improve the method of preparing such 1-dehydro hormones (2). In this paper the authors wish to report a peculiar phenomenon of steroidal fermentation named “pseudo-crystallofermentation “and further suggest a novel and economical process of preparing prednisolone from hydrocortisone on an industrial application. © 1961, Applied Microbiology, Molecular and Cellular Biosciences Research Foundation. All rights reserved.