Two-step one-pot microbial transformation enables obtaining of valuable steroids that are difficult to produce chemically. Here we describe a method for obtaining 11α-hydroxyandrost-4-ene-3,17-dione (11α-HAD) from cheap and available natural sterols (phytosterols or cholesterol).11α-HAD is a primary adrenal steroid in mammals and also a key precursor in the syntheses of halogenated corticoids. Conventional routes for its obtaining are based on chemical synthesis, or microbial hydroxylation of androst-4-ene-3,17-dione (AD). AD in turn is produced primarily with microbial biotransformation of natural sterols by some actinobacteria.Consequent bioconversions of sterols using two microbial strains in one bioreactor vessel without separation and purification of AD provides high yield of 11α-HAD. At the first fermentation step, phytosterol is converted to AD with Mycobacterium neoaurum NRRL 3805B, or relative strains, to yield about 70% (mol/mol). At the second step, AD is almost fully (98%) hydroxylated at the position 11α with Aspergillus ochraceus VKM F-830, or other suitable organisms, in the same bioreactor. At the average, 30% (w/w) of the high-purity crystalline 11α-HAD can be obtained.The method can be exploited for production of 11α-HAD for practical use.

中文翻译：

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从天然甾醇中获得11α-羟基-芳烃-4-烯-3,17-二酮。

两步一锅微生物转化技术使得能够获得难以化学生产的有价值的类固醇。在这里，我们描述了一种从廉价和可用的天然甾醇（植物甾醇或胆固醇）中获得11α-羟基雄烷-4-烯-3,17-二酮（11α-HAD）的方法。11α-HAD是哺乳动物中的主要肾上腺类固醇，也是一种卤代皮质激素合成中的关键前体。获得它的常规途径是基于化学合成或雄烷-4-烯-3,17-二酮（AD）的微生物羟基化。反过来，AD的产生主要是由一些放线菌对天然固醇进行微生物生物转化而产生的。随后，在一个生物反应器容器中使用两种微生物菌株进行固醇的生物转化，而没有AD的分离和纯化，可提供高产量的11α-HAD。在第一步发酵中 用新分枝杆菌NRRL 3805B或相关菌株将植物甾醇转化为AD，产率约为70％（摩尔/摩尔）。在第二步中，AD在同一生物反应器中被曲霉VKM F-830或其他合适的生物体在11α位几乎完全（98％）羟基化。平均可以得到30％（w / w）的高纯度结晶11α-HAD，该方法可用于实际生产11α-HAD。