Microbial side-chain degradation of ergosterol and its 3-substituted derivatives: A new route for obtaining of deltanoids

• Published in: Steroids 2010-10, Vol.75 (10), p.653-658
• Main Authors: Dovbnya, Dmitry V., Egorova, Olga V., Donova, Marina V.
• Format: Article
• Language: English
• Subjects: Androstenediols - chemistry; Androstenediols - metabolism; Bioconversion; Chromatography, Thin Layer; Deltanoids; Ergosterol; Ergosterol - chemistry; Ergosterol - metabolism; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Mycobacterium; Mycobacterium - metabolism; Sitosterols - chemistry; Sitosterols - metabolism; Sterol side-chain degradation
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2010.04.001

The strain of Mycobacterium sp. VKM Ac-1815D was found to convert ergosterol and its 3-acetate mainly to androst-4-ene-3,17-dione (AD) thus demonstrating ability to reduce 7(8)-double bond and hydrolyze sterol ester in addition to oxidation of 3β-hydroxy group, Δ 5-Δ 4 isomerization and side-chain degradation. Ergosterol bioconversion in the presence of isoflavones and ions of some bivalent metals – known inhibitors of 3β-hydroxysteroid dehydrogenase, did not alter products composition. Protection of ergosterol 3β-hydroxyl with methoxymethyl group allowed the formation of bioconversion products retaining the Δ 5,7-configuration. The major product was identified by mass-spectrometry and proton NMR as 3-methoxymethoxy-androsta-5,7-diene-17-one (MA). The MA producing activity was found to be inducible with sterols, cholestenone or lithocholic acid, but not with dehydroepiandrosterone, AD, androsta-1,4-ene-3,17-dione or organic acids. Under the optimized conditions, the yield of MA reached 5 g/l from 10 g/l O-methoxymethyl-ergosterol (approx. 60% molar conversion) for 120 h. The results might be applied at the production of novel vitamin D derivatives.