总状毛霉对4-烯-3-酮甾体的生物转化研究

Microbial transformation of 4-ene-3-one steroids by Mucor racemosus

摘要:

从土样中筛选到一株能转化甾体的菌株,经形态观察,鉴定为总状毛霉(Mucor racemosus)。首次利用该菌株对4-烯-3-酮类甾体衍生物进行生物转化,目的是合成具有潜在活性的羟基类4-烯-3-酮衍生物。转化条件为27℃,220r/min振荡培养4d。转化产物经乙酸乙酯萃取,用硅胶柱层析法分离,通过红外、质谱和核磁分析确定了甾体转化产物的化学结构。黄体酮生物转化得到的产物是14α-羟基-4-孕甾烯-3,20-二酮和7α,14α-二羟基-4-孕甾烯-3,20-二酮;4-雄烯二酮的转化产物是14α-羟基-雄甾-4-烯-3,17-二酮1、4α,17β-二羟基-雄甾-4-烯-3-酮和6α,17β-二羟基-雄甾-4-烯-3-酮。研究结果表明总状毛霉具有转化甾体的能力,对4-烯-3-酮类甾体进行生物转化的主要产物是14α-羟基甾体衍生物。

Abstract:

A steroid-converting fungus isolated from soil samples, was identified as Mucor racemosus according to its morphological characters. The application of M. racemosus for biotransformation of 4-ene-3-one steroids had been investigated to obtain hydroxylated derivatives of 4-ene-3-one steroids. The substrates were incubated with M. racemosus in rotary shaker (220 rpm) culture for a period of four days at 27℃. All of the fermentation media were exhaustively extracted with ethyl acetate and filtered to separate the both from the mycelium. The transformation products were separated on silica gel column chromatography. Each microbial metabolite was characterized by spectroscopic methods such as IR, MS and NMR. Fermentation of progesterone yielded 14α-hydroxypregn-4-en-3,20-dione and 7α,14α-dihydroxypregn-4-en-3,20-dione. Incubation of androstenedione resulted in three transformation products: 14,17-dihydroxyandrost-4-en-3-one, 14α,17β-dihydroxyandrost-4-en-3-one and 6α,17β-dihydroxyandrost-4-en-3-one. This fungus was found to biotransformation steroids. The results showed that the fermentation of 4-ene-3-one steroids with M. racemosus yielded mainly 14α-hydroxy steroids.