Microbial Baeyer-Villiger oxidation of steroidal ketones using Beauveria bassiana: Presence of an 11α-hydroxyl group essential to generation of D-homo lactones

This paper demonstrates for the first time transformation of a series of 17-oxo steroidal substrates (epiandrosterone, dehydroepiandrosterone, androstenedione) by the most frequently used whole cell biocatalyst. Beauveria bassiana, to 11 alpha-hydroxy-17a-oxa-D-homo-androst-17-one products, in the following sequence of reactions: 11 alpha-hydroxylation and subsequent Baeyer-Villiger oxidation to a ring-D lactone. 11 alpha-Hydroxyprogesterone, the product of the first stage of the progesterone metabolism, was further converted along two routes: hydroxylation to 6 beta,11 alpha-dihydroxyprogesterone or 17 beta-acetyl chain degradation leading to 11 alpha-hydroxytestosterone. the main metabolite of the substrate. Part of 11 alpha-hydroxytestosterone underwent a rare reduction to 11 alpha-hydroxy-5 beta-dihydrotestosterone. The experiments have demonstrated that the Baeyer-Villiger monooxygenase produced by the strain catalyzes solely oxidation of C-20 or C-17 ketones with 11 alpha-hydroxyl group. 17-Oxo steroids, beside the 11 alpha-hydroxylation and Baeyer-Villiger oxidation, also underwent reduction to 17 beta-alcohols: activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) has significant impact on the amount of the formed ring-D delta-lactone. (C) 2011 Elsevier B.V. All rights reserved.