短刺小克银汉霉菌11β羟化环氧黄体酮研究  

11β-Hydroxylation of 16α,17α-Epoxyprogesterone by Cunninghamella blakesleeana ATCC 8688a

作　　者：吴冬香[1] 李久红[1] 王海清[1] 关怡新[1] 姚善泾[1] 

机构地区：[1]浙江大学化学工程与生物工程学系,浙江杭州310027

出　　处：《高校化学工程学报》2012年第1期77-83,共7页Journal of Chemical Engineering of Chinese Universities

基　　金：浙江省科技计划项目(2005C31028)

摘　　要：采用短刺小克银汉霉菌(Cunninghamella blakesleeana ATCC 8688a)催化底物环氧黄体酮进行11位羟基化反应,将转化产物分离纯化得到晶体,经过质谱、红外光谱和核磁共振氢谱表征,结合产物的比旋光度测定,证实霉菌催化转化主产物是11β-羟基-16α,17α-环氧孕甾-4-烯-3,20-二酮。对霉菌发酵转化的培养基组成、操作条件和投料方式等进行了考察,确定了比较适宜的工艺条件,在2 g.L.1投料浓度下,环氧黄体酮的11β羟化产物得率稳定在35%左右;采取发酵液稀释补料投料方式,可有效地将产物得率从35%提高到43%。利用C.blakesleeana成功地实现了直接11β羟化环氧黄体酮,为甾体糖皮质激素类药物的生产提供了一条简化的合成路线。Cunninghamella blakesleeana ATCC 8688a was used to catalyze the 11β-hydroxylation of 16α,17α-epoxyprogesterone and the conversion product was purified and characterized by ESI,IR and NMR spectroscopy,respectively.The characterization results combining with the specific optical rotation determination of the purified product indicate that the main product is 11β-hydroxy-16α,17α-epoxy-pregna-4-ene-3,20-dione.Then the medium composition,operation conditions and feeding mode of substrate were investigated.At optimized experimental conditions,the yield of product is stabilized at 35% with 2 g？L？1 feed concentration.By fed-batch culture,the yield of product increased efficiently to 43%.C.blakesleeana successfully performs the 11β-hydroxylation on the substrate directly,and it provides a simplified synthesis route to hormone pharmaceuticals industry.

关 键 词：短刺小克银汉霉菌 生物催化 甾体 环氧黄体酮 11β羟化 

分 类 号：O643[理学—物理化学] TQ467.95[理学—化学]