Hydroxylation of DHEA and its analogues by Absidia coerulea AM93. Can an inducible microbial hydroxylase catalyze 7α- and 7β-hydroxylation of 5-ene and 5α-dihydro C19-steroids? |
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| Institution: | 1. Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon;2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;4. Department of Biology, University of Balamand, Koura 100, Lebanon;5. Department of Biochemistry, Faculty of Science, King Abdulaziz Universisty. Jeddah 21412, Saudi Arabia;1. Department of Pharmacy, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, Shanghai, China;2. The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;3. Department of Anesthesiology & Zhejiang Province Key Laboratory of Anesthesiology, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;1. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;2. Atta-ur-Rahman Institute for Natural Products Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;3. Department of Basic Sciences, DHA Suffa University, Off, Khayaban-e-Tufail, Phase VII (Extension), DHA, Karachi 75500, Pakistan;4. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;1. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia;2. Medicinal Chemistry, Monash Institute of Pharmaceutical Science, Monash University, 381 Royal Parade, Parkville 3052, Australia;3. Department of Biology, University of Utah, Salt Lake City, UT 84112, United States;4. School of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia;1. School of Marine Science and Engineering, Hebei University of Technology, Tianjin 300130, China;2. State Research Center of Industrialization for Crystallization Technology, School of Chemical Engineering and technology, Tianjin University, Tianjin 300072, China;3. School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China;4. College of Chemical and Pharmaceutical Engineering, Hebei Universtity of Science and Technology, Shijiazhuang 050018, China |
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| Abstract: | In this paper we focus on the course of 7-hydroxylation of DHEA, androstenediol, epiandrosterone, and 5α-androstan-3,17-dione by Absidia coerulea AM93. Apart from that, we present a tentative analysis of the hydroxylation of steroids in A. coerulea AM93. DHEA and androstenediol were transformed to the mixture of allyl 7-hydroxy derivatives, while EpiA and 5α-androstan-3,17-dione were converted mainly to 7α- and 7β-alcohols accompanied by 9α- and 11α-hydroxy derivatives. On the basis of (i) time course analysis of hydroxylation of the abovementioned substrates, (ii) biotransformation with resting cells at different pH, (iii) enzyme inhibition analysis together with (iv) geometrical relationship between the C–H bond of the substrate undergoing hydroxylation and the cofactor-bound activated oxygen atom, it is postulated that the same enzyme can catalyze the oxidation of C7-Hα as well as C7-Hβ bonds in 5-ene and 5α-dihydro C19-steroids. Correlations observed between the structure of the substrate and the regioselectivity of hydroxylation suggest that 7β-hydroxylation may occur in the normal binding enzyme-substrate complex, while 7α-hydroxylation—in the reverse inverted binding complex. |
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| Keywords: | DHEA metabolism Dehydroepiandrosterone 7-hydroxylase Enzymatic steroid hydroxylation Hydroxy-DHEA Hydroxy-epiandrosterone |
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