Biotechnological Transformation of Hydrocortisone into 16α-Hydroxyprednisolone by Coupling Arthrobacter simplex and Streptomyces roseochromogenes

Abstract

16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by <i>Arthrobacter simplex</i><i>ATCC</i>31652 with a 16α-hydroxylation reaction by <i>Streptomyces roseochromogenes ATCC</i>13400. In this study we tested, for the first time, potential approaches to couple the two reactions using similar pH and temperature conditions for hydrocortisone bioconversion by the two strains. The <i>A. simplex</i> capability to 1,2-dehydrogenate the 16α-hydroxyhydrocortisone, the product of <i>S. roseochromogenes</i> transformation of hydrocortisone, and vice versa the capability of <i>S. roseochromogenes</i> to 16α-hydroxylate the prednisolone were assessed. Bioconversions were studied in shake flasks and strain morphology changes were observed by SEM. Whole cell experiments were set up to perform the two reactions in a sequential mode in alternate order or contemporarily at diverse temperature conditions. <i>A. simplex</i> catalyzed either the dehydrogenation of hydrocortisone into prednisolone efficiently or of 16α-hydroxyhydrocortisone into 16α-hydroxyprednisolone in 24 h (up to 93.9%). Surprisingly <i>S. roseochromogenes</i> partially converted prednisolone back to hydrocortisone. A 68.8% maximum of 16α-hydroxyprednisolone was obtained in 120-h bioconversion by coupling whole cells of the two strains at pH 6.0 and 26 °C. High bioconversion of hydrocortisone into 16α-hydroxyprednisolone was obtained for the first time by coupling <i>A. simplex</i> and <i>S. roseochromogenes</i>.