Phylogenetic Studies,Gene Cluster Analysis,and Enzymatic Reaction Support Anthrahydroquinone Reduction as the Physiological Function of Fungal 17β‐Hydroxysteroid Dehydrogenase |
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| Authors: | Leon Fürtges David Conradt Dr. Michael A. Schätzle Shailesh Kumar Singh Dr. Nada Kraševec Prof. Dr. Tea Lanišnik Rižner Prof. Dr. Michael Müller Dr. Syed Masood Husain |
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| Affiliation: | 1. Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universit?t Freiburg, Freiburg, Germany;2. Roche Pharma AG, Grenzach-Wyhlen, Germany;3. Centre of Biomedical Research, SGPGIMS Campus, Uttar Pradesh, India;4. National Institute of Chemistry, Ljubljana, Slovenia;5. Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia |
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| Abstract: | 17β‐Hydroxysteroid dehydrogenase (17β‐HSDcl) from the filamentous fungus Curvularia lunata (teleomorph Cochliobolus lunatus) catalyzes NADP(H)‐dependent oxidoreductions of androgens and estrogens. Despite detailed biochemical and structural characterization of 17β‐HSDcl, its physiological function remains unknown. On the basis of amino acid sequence alignment, phylogenetic studies, and the recent identification of the physiological substrates of the homologous MdpC from Aspergillus nidulans and AflM from Aspergillus parasiticus, we propose an anthrahydroquinone as the physiological substrate of 17β‐HSDcl. This is also supported by our analysis of a secondary metabolite biosynthetic gene cluster in C. lunata m118, containing 17β‐HSDcl and ten other genes, including a polyketide synthase probably involved in emodin formation. Chemoenzymatic reduction of emodin by 17β‐HSDcl in the presence of sodium dithionite verified this hypothesis. On the basis of these results, the involvement of a 17β‐HSDcl in the biosynthesis of other anthrahydroquinone‐derived natural products is proposed; hence, 17β‐HSDcl should be more appropriately referred to as a polyhydroxyanthracene reductase (PHAR). |
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| Keywords: | anthrahydroquinones asymmetric synthesis enzyme catalysis gene annotation oxidoreductases |
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