Biohydroxylation of 7-oxo-DHEA, a natural metabolite of DHEA, resulting in formation of new metabolites of potential pharmaceutical interest

• Published in: Chemical biology & drug design Vol. 88; no. 6; pp. 844 - 849
• Main Authors: Świzdor, Alina, Panek, Anna, Milecka-Tronina, Natalia
• Format: Journal Article
• Language: English
• Published: HOBOKEN Blackwell Publishing Ltd 01.12.2016; Wiley
• Subjects: 7-oxo-DHEA; Biochemistry & Molecular Biology; Biotransformation; biotransformations; Chemistry, Medicinal; Dehydroepiandrosterone - analogs & derivatives; Dehydroepiandrosterone - metabolism; DHEA; Hydroxylation; hydroxylations; Life Sciences & Biomedicine; Mucorales - metabolism; Pharmaceutical Preparations; Pharmacology & Pharmacy; Science & Technology; Spectrum Analysis - methods; Syncephalastrum racemosum; DHEA; hydroxylations; URSOLIC ACID; BIOTRANSFORMATION; biotransformations; STEROIDS; Syncephalastrum racemosum; HYDROXYLATION; 7-oxo-DHEA; DEHYDROEPIANDROSTERONE
• ISSN: 1747-0277; 1747-0285; 1747-0285
• DOI: 10.1111/cbdd.12813

Metabolism of steroids in healthy and unhealthy human organs is the subject of extensive clinical and biomedical studies. For this kind of investigations, it is essential that the reference samples of new derivatives of natural, physiologically active steroids (especially those difficult to achieve in the chemical synthesis) become available. This study demonstrated for the first time transformation of 7‐oxo‐DHEA—a natural metabolite of DHEA, using Syncephalastrum racemosum cells. The single‐pulse fermentation of substrate produced two new hydroxy metabolites: 1β,3β‐dihydroxy‐androst‐5‐en‐7,17‐dione and 3β,12β‐dihydroxy‐androst‐5‐en‐7,17‐dione, along with the earlier reported 3β,9α‐dihydroxy‐androst‐5‐en‐7,17‐dione and 3β,17β‐dihydroxy‐androst‐5‐en‐7‐one. Simultaneously, the same metabolites, together with small quantities of 7α‐ and 7β‐hydroxy‐DHEA, as well as the products of their reduction at the C‐17 were obtained after transformation of DHEA under pulse‐feeding of the substrate. The observed reactions suggested that this micro‐organism contains enzymes exhibiting similar activity to those present in human cells. Thus, the resulting compounds can be considered as potential components of the eukaryotic, including human, metabolome. New oxygenated metabolites of biologically active 7‐oxo‐DHEA were formed by fungal stereoselective hydroxylations by Syncephalastrum racemosum. The studies demonstrated that the obtained derivatives may be simultaneously the final metabolites of DHEA. The observed reactions suggested that this micro‐organism contains enzymes exhibiting similar activity to those present in human cells. The resulting compounds can be considered as potential components of the eukaryotic, including human, metabolome.