改进底物添加体系制备氢化可的松

Biotransformation RSA to hydrocortisone:improvement of adding substrate

在蓝色梨头霉和新月弯孢霉协同转化制备氢化可的松(HC)过程中,常规的底物热溶液体系由17α羟基孕甾4-烯-3,20-二酮-21-醋酸酯(RSA)和乙醇组成,其中m(RSA)∶V(乙醇)=1∶25;改进后的底物溶液体系由Tween-80、丙三醇、RSA和磷酸盐缓冲溶液(PBS)组成,其中V(Tween-80)∶V(丙三醇)∶m(RSA)∶V(PBS)=1∶3∶1∶25。RSA质量浓度从2g/L起,累加到5g/L,RSA全部被转化,且产物氢化可的松(HC)产率与常规低浓度投料相当;在RSA质量浓度3g/L时添加底物,协同菌丝体能重复利用达3次,HC产率稳定在70%左右;经3批次实验室摇瓶放大制备实验,产物HC平均收率为52%,重现性较好,工艺操作稳定。Tween-80/丙三醇/RSA/PBS底物体系较常规RSA/乙醇构成的底物添加体系,可显著提高HC生产收率,有工业应用价值。

The selected mode of Tween-80/glycerol/RSA/PBS（v（Tween-80）∶v（glycerol）∶w（RSA）∶v（PBS）=1∶3∶1∶25）for addition of the substrate RSA was developed.The mode was used in the procedure of the bioconversion from RSA to HC by cooperative mycelia Abisidia coerulea and Curvularia lunata,making the substrate concentration accumulated in the media be up to 5 g/L with the considerable yield of HC,compared with the 2 g/L in the traditional one with the type of RSA/ethanol（w（RSA）∶v（ethanol）=1∶25）.The concentration of the substrate RSA was 3 g/L,the system of the cooperative mycelia media could be repeatedly used 3 times with the HC produced yield of 70% in a preparative-scale experiment at the gram level,the recovery ratio of product HC from RSA was up to 52%.The novel mode of addition substrate in the bioconversion process showed a reproducible and stable process.