Biotransformation of Hydrocortisone by Mucor hiemalis and In silico Study of the Produced Metabolite against 11β-Hydroxysteroid Dehydrogenase Type I

Background: Microbial biotransformation of steroids is a valuable method for producing active pharmaceuticals or potentially active steroids, and fungi serve as pow-erful biocatalysts in this process. On the other hand, in silico analyses are preliminary yet influential studies for the evaluation of compounds in the drug development process. Objective: This study aimed to examine the ability of Mucor hiemalis to biotransform hydrocortisone, predict the potential binding ability of the products to the 11β-hydroxysteroid dehydrogenase enzyme (as a target for the control of diabetes mellitus type 2), and assess the products’ pharmacokinetic properties. Methods: The incubation of M. hiemalis with hydrocortisone for nine days resulted in the production of a main product in the culture medium. The metabolite was subsequently isolated using chromatographic procedures and its identity was determined by spectroscopic analysis. Computational binding studies and pharmacokinetic profile prediction of the metabolite were conducted using AutoDock Vina and SwissADME, respectively. Results: The biotransformation of hydrocortisone by M. hiemalis produced 11β,17α,20β,21-tetrahydroxypregn-4-en-3-one as the major metabolite. Molecular dock-ing studies demonstrated that the metabolite can interact with functional residues located at the catalytic site of the enzyme in different ways. Furthermore, the results indicated a favorable pharmacokinetic profile of the produced metabolite. Conclusion: The current study showed that M. hiemalis may be considered an effective tool for the biotransformation of steroids and the production of potentially bioactive compounds.