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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。
Statin is a pleiotropic drug with a wide range of important pharmacological actions that significantly reduce blood cholesterol levels and prevent atherosclerosis and coronary heart disease. Statins include natural compounds and their derivatives and fully synthetic compounds. Natural Statins are a kind of hydroxy valerolactone substituted hexahydronaphthalene compounds, including Compactin and its semi-synthetic derivatives Pravastatin and Lovastatin and their semi-synthetic derivatives Simv-astatin. Commercial production of Lovastatin and Compactin is a deep liquid fermentation process based on Aspergillus terreus and Penicillium citrinum, respectively, and Pravastatin is obtained from the biosynthesis of Compactin by Streptonyces carbophilus. Biotechnological methods have been applied to Simvastatin research and production, cloning the A. terreus lovD gene and overexpression in E. coli to produce acyltransferases that specifically transfer dimethylbutyryl groups to Monacolin J C8 hydroxyl Simvastatin was generated.