G.K. Skryabin Institute of Biochemistry & Physiology of Microorganisms Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
Steroids. 2010 Oct;75(10):653-8. doi: 10.1016/j.steroids.2010.04.001. Epub 2010 Apr 10.
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 3beta-hydroxy group, Delta(5)-Delta(4) isomerization and side-chain degradation. Ergosterol bioconversion in the presence of isoflavones and ions of some bivalent metals - known inhibitors of 3beta-hydroxysteroid dehydrogenase, did not alter products composition. Protection of ergosterol 3beta-hydroxyl with methoxymethyl group allowed the formation of bioconversion products retaining the Delta(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 5g/l from 10g/l O-methoxymethyl-ergosterol (approx. 60% molar conversion) for 120h. The results might be applied at the production of novel vitamin D derivatives.
从分枝杆菌菌株 VKM Ac-1815D 中发现，它可以将麦角甾醇及其 3-醋酸酯主要转化为雄甾-4-烯-3,17-二酮 (AD)，从而显示出除了氧化 3β-羟基、Δ(5)-Δ(4)异构化和侧链降解外，还具有还原 7(8)-双键和水解甾醇酯的能力。在异黄酮和一些二价金属离子的存在下，麦角甾醇的生物转化并没有改变产物的组成。麦角甾醇 3β-羟基用甲氧基甲基保护后，可以形成保留Δ(5,7)-构型的生物转化产物。主要产物通过质谱和质子 NMR 鉴定为 3-甲氧基甲氧基-雄甾-5,7-二烯-17-酮 (MA)。发现该 MA 产生活性可诱导甾醇、胆固醇酮或胆酸，但不能诱导脱氢表雄酮、AD、雄甾-1,4-烯-3,17-二酮或有机酸。在优化条件下，从 10g/l 的 O-甲氧基甲基麦角甾醇（约 60%摩尔转化率）中，经过 120 小时的反应，MA 的产量达到了 5g/l。这些结果可能应用于新型维生素 D 衍生物的生产。
