Biotransformation of prednisolone to hydroxy derivatives by Penicillium aurantiacum

Prednisolone, a synthetic adrenal corticosteroid drug, is known to have anti-inflammatory and autoimmune activity. Biotransformation of prednisolone was carried out to obtain more bioactive prednisolone derivatives. Among six different fungi, Penicillium aurantiacum proved to be the best prednisolone hydroxylator. As a result of prednisolone biotransformation by P. aurantiacum, whole cells four different prednisolone derivatives were investigated. 20β-Hydroxyprednisolone (1) and 21,21-dimethoxy-11β-hydroxypregn-1,4-dien-3,20-dione (2) were detected as the main metabolites. These metabolites together with other two metabolites, 11β-hydroxyandrost-1,4-dien-3,17-dione (3) and 11β,17β-dihydroxyandrost-1,4-dien-3- one (4), were purified and assigned by an interpretation of their spectral data using mass spectroscopy (MS), proton nuclear magnetic resonance (¹H-NMR), carbon nuclear magnetic resonance (¹³C-NMR) and infrared spectroscopy (IR) analyses. The best fermentation conditions for production of compounds 1–4 were as follows: medium (3) consisting of (g/l): glucose 20; l-asparagine 0.7; MgSO₄.7H₂O 0.5; KH₂PO₄ 1.52; KCl 0.52; Cu (NO₃)₂ traces; ZnSO₄.7H₂O traces, supplemented with prednisolone concentration of 0.3?mg/ml, inoculated by 10% of microorganism and incubated for 72?h. Under these optimized conditions, ～94.8% of the added prednisolone was converted to aforementioned derivatives, which have the potential to be used in industrial production of important pharmaceutical compounds.