微生物转化辛伐他汀及产物结构的鉴定  

Microbial conversion of simvastatin and identification of its product

作　　者：彭丹妮[1] 黄静[1] 厉铭[2] 顾君琳[2] 刘坚[1] 杨琍苹[2] 吴自荣[1] 

机构地区：[1]华东师范大学生命科学学院,上海200062 [2]华东师范大学化学系,上海200062

出　　处：《西北农林科技大学学报（自然科学版）》2008年第2期153-158,共6页Journal of Northwest A&F University(Natural Science Edition)

基　　金：上海市科委2004年重大计划项目(04DZ19207-1)

摘　　要：【目的】用微生物转化获得辛伐他汀羟基化衍生物,为降胆固醇药物的开发奠定基础。【方法】用自养诺卡氏菌堪培拉亚种转化辛伐他汀,并研究助溶剂、投料时间、底物、温度、pH等对其转化率的影响。【结果】获得最佳发酵条件为:自养诺卡氏菌堪培拉亚种培养36 h后加入由丙酮处理的辛伐他汀溶液,转化pH为7.5,温度28℃,且在有辛伐他汀诱导时,转化率高。转化产物经纯化鉴定,初步确定其为6-羟甲基-辛伐他汀。【结论】成功获得了辛伐他汀羟基化衍生物——6-羟甲基-辛伐他汀。[Objective] The purpose of this study is to obtain hydroxy derivative of simvastatin by microbial conversion to get new potent drugs for lowing cholesterol. [Method] Simvastatin was transformed to hydroxy derivative by strain Nocardia autotrophica subsp, canberrica ATCC 35203. To obtain the optimal fermentation conditions,the conversion conditions,which affected hydroxylation such as different kinds of solubilizers,time adding simvastatin,substrate, temperature and pH were investigated. [Result] The results showed that the productivity was maximized when strain ATCC 35203 was incubated at 28 ℃,with induction of simvastatin at the beginning,and then after 36 hours of growth,simvastatin treated with acetone was added and the incubation was continued in the medium with pH 7.5. The bioconverted product was purified and its structure was further identified as 6-hydroxymethyl-simvastatin on the basis of spectral data（MS and 1H NMR）. [Conclusion] Simvastatin＇s hydroxy derivative was obtained successfully.

关 键 词：自养诺卡氏菌堪培拉亚种 辛伐他汀 6-羟甲基-辛伐他汀 HMG—CoA还原酶抑制剂 微生物转化 

分 类 号：Q933[生物学—微生物学]