Department of Chemistry, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland.
Molecules. 2020 Sep 15;25(18):4226. doi: 10.3390/molecules25184226.
The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields.
甾体化合物的生物转化是一种有前途的、环保的方法，可以用于制备新的药物和激素。在甾体类化合物的代谢途径中，常见的反应类型之一是拜耳-维利格氧化反应，该反应会导致环酮如甾体转化为内酯。已证明真菌酶催化该反应的 Baeyer-Villiger 单加氧酶 (BVMO) 具有广泛的底物范围、选择性和催化性能，可与化学氧化相媲美，具有更高的环境友好性。本研究涵盖了一系列雄烷甾体（表雄酮和雄酮）和雄烯甾体（孕酮、孕烯醇酮、脱氢表雄酮、雄烯二酮、19-OH-雄烯二酮、睾酮和 19-去甲睾酮）的生物转化，这些甾体是由丝状真菌 AM110 进行培养转化的。通过 GC 监测转化过程，并根据色谱和光谱数据鉴定生成的产物。研究发现，该真菌对底物进行有效的 Baeyer-Villiger 氧化。有趣的是，在雄烯二酮骨架中引入 19-OH 基团对 BVMO 活性有显著的抑制作用，因为 10 天的转化会留下一半的 19-OH-雄烯二酮未反应。表雄酮和雄酮是研究化合物中唯一的 5α-饱和底物，它们的代谢途径更为复杂。这两种底物的转化与时间进程监测相结合，揭示了每个底物都转化为三种产物，对应于 C-3 和 C-17 的氧化，具有不同的时间分布和产率。
