Side-chain cleavage and C-20 ketone reduction of hydrocortisone by a natural isolate ofChroococcus dispersus |
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Authors: | Younes Ghasemi Mohammad Ali Faramarzi Mojdeh Arjmand-Inalou Abdolali Mohagheghzadeh Shadman Shokravi Mohammad Hossein Morowvat |
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Affiliation: | 1. Faculty of Pharmacy and Pharmaceutical Science Research Center, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran 2. Department of Pharmaceutical Biotechnology, Biotechnology Research Center, Faculty of Pharmacy, Medical Sciences University of Tehran, P.O. Box 14155-6451, 14174, Tehran, Iran 3. Department of Biology, Institute of Applied Sciences, Iranian Center of Culture and Education, Shahid Beheshti University, P.O. Box 19835-371, Tehran, Iran
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Abstract: | A unicellular cyanobacterium,Chroococcus dispersus (Keissl.) Lemmermann, was isolated from paddy-field and tested in biotransformation experiments of hydrocortisone (compound 1). This strain has not been previously examined for steroid substance modification. Fermentation was carried out in BG-11 medium supplemented with 0.05% substrate at 25 °C for seven days incubation. The metabolites were chromatographically purified and characterised using spectroscopic methods. The fermentation yielded 11β,17α,20β,21-tetrahydroxypregn-4-en-3-one (compound 2), 11β,17β-dihydroxyandrost-4-en-3,17-dione (compound 3), and 11β-hydroxyandrost-4-en-3,17-dione (compound 4). Bioreaction characteristics observed were 20-ketone reduction for accumulation of compound 2 and side chain degradation of the substrate to give compounds 3 and 4. Time course study showed the accumulation of the product 2 from the second day of the fermentation and product 3 as well as product 4 from the third day. All the metabolites reached their maximum concentration in seven days. Aeration and continuous light or light duration (16/8 hours light/dark) have no effect on the transformation yield. Optimum concentration of the substrate, which gave maximum bioconversion efficiency, was 0.5 mg ml?1 in the transformation experiment. Growth was not influenced by the addition of steroid substrate. Biotransformation was completely inhibited when steroid concentration was above 2.0 mg ml?1. |
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