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机构地区:[1]兰州交通大学化学与生物工程学院,甘肃兰州730070
出 处:《药物生物技术》2011年第6期563-568,共6页Pharmaceutical Biotechnology
基 金:教育部"春晖"计划(Z2006-1-6213);国家自然科学基金(30960063)资助
摘 要:Statin类化合物是一种多效药物,具有广泛的重要药理作用,能显著降低血胆固醇脂,预防动脉粥样硬化和冠心病发生。Statin类化合物包括天然化合物及其衍生物和全合成化合物两类,天然Statin是一类羟基戊酸内酯取代的六氢萘化合物,包括Compactin及其半合成衍生物Pravastatin和Lovastatin及其半合成衍生物Simv-astatin。Lovastatin和Compactin的工业化生产是分别基于Aspergillus terreus和Penicillium citrinum的液体深层发酵工艺,Pravastatin可由Streptonyces carbophilus生物转化Compactin获得。生物技术方法已经应用于Simvastatin研究与生产,克隆A.terreus lovD基因并在E.coli中过表达产生酰基转移酶,该酶能专一性地将二甲基丁酰基团转到Monacolin J C8羟基上生成Simvastatin。Statins have the multiple biological effects and pharmacological functions. They selectively inhibit HMG-CoA reductase, the regulatory and rate-limiting enzyme in cholesterol biosynthesis,lowering cholesterol level in blood and preventing plaque buildup inside the arteries. Moreover,statins become the preventive drugs for cardiovascular disease and reduce the risk for atherosclerosis and coronary artery disease. Statins include natural statins with their semisynthetic derivatives and fully synthetic statins. The main natural statins are compactin, lovastatin and their derivatives pravastatin and simvastatin. All natural statins are substituted hexa- hydronaphthalene lactones. The industrial production of lovastatin and compactin is based on Aspergillus terreus and Penicillium citri- aura batch fermentation. Pravastatin is normally produced by biotransformation of eompactin by Streptomyces carbophilus. Recently, more attention has been paid to the production of pravastatin by biotechnologieal processes. Cloned lovD gene from A. terreus and overexpressed it in E. coli, acyhransferase, the production of lovD, can be obtained. This enzyme selectively transfers the dimethylbutyryl group into the C8 hydroxyl group of monacolin J to yield simvastatin.
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