Premium
Phylogenetic Studies, Gene Cluster Analysis, and Enzymatic Reaction Support Anthrahydroquinone Reduction as the Physiological Function of Fungal 17β‐Hydroxysteroid Dehydrogenase
Author(s) -
Fürtges Leon,
Conradt David,
Schätzle Michael A.,
Singh Shailesh Kumar,
Kraševec Nada,
Rižner Tea Lanišnik,
Müller Michael,
Husain Syed Masood
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600489
Subject(s) - aspergillus nidulans , polyketide , biology , biochemistry , polyketide synthase , hydroxysteroid dehydrogenases , gene cluster , dehydrogenase , biosynthesis , reductase , gene , enzyme , mutant
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).