Steroid Bioconversion

Abstract

Steroids constitute a particular class of lipids characterized by a typical tetracyclic skeleton, composed of one five‐member ring and three fused six‐member rings. Steroids are widely used as therapeutic agents and since their inception in the market, research efforts have been made in order to improve production processes as well as to develop novel synthetic molecules, with enhanced efficiency and reduced side effects. Given the complexity of the steroid skeleton, total chemical synthesis of given steroid molecules is hardly an effective approach; hence, steroid production processes rely on chemical modifications of educts that structurally resemble the targeted product. Still, steroid molecules present multiple chiral centers, a feature that makes particularly appealing the use of the selective microbial catalysts to provide a pathway that does not require protection, and additional deprotection steps. Furthermore, bioconversions are performed in a milder, greener environment, as compared to the purely chemical approach. The present work aims to provide an overview of steroid bioconversions. The potential of biologic agents (microbial cells/enzymes) to catalyze the conversion of a wide array of steroid educts will be presented, with particular emphasis on those that have achieved particular relevance, as well as on key aspects within the field. The chapter ends with the perspective trends in the field of steroid bioconversions

Recent Advances in Biotechnology in Animal Health

“…After Marker's success story, in year 1951, a microbial process of converting oxidized progesterone to cortisone was introduced by scientists at another Mexican company, the Upjohn Co., using Syntex's progesterone (Bohning and Morris 1999). Since then, the industrial production of steroidal hormones and drugs, which are otherwise difficult to obtain through conventional methods, has become the best known application of microbial biotransformation (Fernandez et al 2003;Fernandez and Cabral 2010;Vom Steeg and Klein 2017;Cano-Flores et al 2020). Figure 6 shows how bacteria are utilized to produce recombinant bovine somatotropin (rBST) (Shakweer 2008); rBST is administered to increase milk production in dairy cows and improve feed efficiency as well.…”

Biotransformation of Steroids Using Different Microorganisms

“…An efficient regio-and stereoselectivity was observed in the biotransformation of 1 on a large scale by the system Mucor 881 (M881) to give the hydroxylated derivatives 6, 6β,11α-dihydroxyprogesterone (20), and 6β-hydroxypregn-4-ene-3,11,20-trione (21). In the literature, it is described that species of the genus Mucor and Rhizopus can hydroxylate said positions but with lower yields.…”

“…The physiological activity of steroids depends on their structure, the type, number, spatial orientation, and reactivity of the different functional groups present in the tetracyclic core as well as the oxidation state of the rings. For example, the presence of an oxygenated function in C-11β is crucial for the anti-inflammatory activity; the hydroxyl function in C-17β determines androgenic properties; the aromatization of ring A confers estrogenic effect; and corticosteroids have the 3-keto-4-ene group and the pregnane side chain at C-17 [21,22].…”

“…The production of steroid drugs and hormones is one of the best examples of the applications that biotransformations have on an industrial scale [3,21]. Microbiological transformations are an effective tool for the preparation of various compounds [26], which can be difficult to obtain by conventional chemical methods and have been widely used in the bioconversion of steroids [25].…”

“…Currently, a great versatility of microbial systems in the pharmaceutical industry for the commercial production of steroids and other drugs is recognized [27,28]. Several hundreds of microbiological transformations of steroids have been reported in the literature; also, many bioconversions have been incorporated into numerous partial syntheses of new compounds for their evaluation such as hormones or drugs [21,[29][30][31][32]. Chemical derivatives of some steroids are reported to have better therapeutic advantages than the starting materials.…”