微生物转化雄甾-4-烯-3,17-双酮的菌种筛选和转化条件的初步研究

Microbial Hydroxylation of Androst-4-ene-3,17-dione I:Screening of Strains and Study of the Transformation Conditions

雄甾-4-烯-3,17-双酮(简称4AD)是甾体药物的重要中间产物,其11α羟化产物可制成治疗心血管疾病的药物。通过对30株不同种属真菌转化4AD能力的筛选,获得球孢白僵菌(Beauveria bassiana)QY2A对4AD有高效C11α羟化能力,得到目标产物C11α-羟基雄甾-3,17-双酮(简称11α-OH-4AD)。另对该菌株的转化条件进行优化,结果表明:初始pH值6.0,温度28℃,转速180r/min,转化时间60h,助溶剂甲醇终浓度和底物浓度分别为2.5%和2.5g/L时,11α-OH-4AD的转化率为65%,比未优化的转化率提高了51.2%。

Microbial hydroxylation of androst-4-ene-3, 17-dione（4AD） was investigated in this study. The hydroxylated product of 4AD, 11α- hydroxyandrnst-4-ene-3,17-dione （11α-OH-4AD） is valuable intermediate in the synthesis of pharmaceuticals. 30 different species and strains of fungi were screened for their biotransformation ability. It was found that Beauveria bass/ana QY2A strain significantly showed the high 11α hydroxyalate efficiency and transformate 4AD to the target product 11α-OH-4AD which had been purified and identified.The hydroxylation condition of 4AD by B. bassiana QY2A was studied. The optimum transformation conditions were obtained： the initial pH value of 6.0, temperature 28℃, 180r/min, the transformation time 60h, the concentration of solution and substrate were 2.5% and 2.5g/L respectively. Then the conversion yield of 11α-OH-4AD was 65%, increased by 51.2%.