微乳体系中11β-羟基甲羟孕酮的C1,2生物脱氢

Biodehydrogenation of 11β-hydroxyl medroxyprogesterone by Arthrobacter simplex UR016 in microemulsion system

摘要:

为改善过程传质, 提高甾类药物中间体11β-羟基甲羟孕酮C1, 2生物脱氢转化率, 采用简单节杆菌Arthrobacter simplex UR016菌株在Tween-80/乙醇/食油/水构成的微乳体系中进行生物脱氢, 并考察了微乳体系组成、转化温度、投料浓度对脱氢反应的影响。结果表明: 以菌体培养液作为水相, 食油作为油相构建微乳体系, 食油最适加量为10 g/L, 表面活性剂Tween-80加量为4 g/L; 底物经醇溶后水析投料, 乙醇最适加量为发酵液体积的7% (V/V); 最适转化温度为33°C; 当底物浓度为4 g/L时, 在构建的微乳体系中转化46 h, 脱氢转化率达88.6%, 与水相转化工艺相比提高了66.2%。在该体系中疏水性11b-羟基甲羟孕酮底物得到了有效的增溶和扩散, 生物脱氢转化率明显提高。

Abstract:

To improve mass transfer and enhance the yield for C1,2 biodehydrogenation of steroid 11β-hydroxyl medroxyprogesterone, we carried out the dehydrogenation reaction of 11β-hydroxyl medroxyprogesterone in an oil-in-water (O/W) microemulsion by Arthrobacter simplex UR016. We studied the effects of system composition, dehydrogenation temperature and substrate concentration on microbial transformation. We formulated a suitable O/W microemulsion system with Arthrobacter simplex UR016 culture broth as aqueous phase, 10 g/L of edible oil as oil phase, 4 g/L of Tween-80 and 7% (V/V) alcohol as surfactant and cosurfactant. The optimal dehydrogenation temperature was 33°C. The results showed that in Tween-80/alcohol/edible oil/water microemulsion system, the hydrophobic steroid was solubilised and diffused effectively, with the maximum conversion rate of 88.6% at 46 h under 4 g/L substrate concentration, an increase of 66.2% compared to that in aqueous system. The C1,2 biodehydrogenation of 11b-hydroxyl medroxyprogesterone is more efficient in water-edible oil microemulsion system than in aqueous system.