辛伐他汀的生物合成

Biosynthesis of Simvastatin – a mini-review

摘要:

辛伐他汀是洛伐他汀的半合成衍生物, 传统的生产工艺是以洛伐他汀为原料, 经化学合成得到辛伐他汀。洛伐他汀的直接甲基化方法已成为目前生产上使用最多的工艺路线。化学合成工艺的不足之处乃在于化学法合成过程中, 反应条件苛刻, 副反应多, 产品分离纯化难度大以及来自环保和劳动保护的压力。近年来, 随着洛伐他汀生物合成途径研究的深入, 人们已经将更多的注意力转向辛伐他汀的生物合成。就辛伐他汀侧链的化学水解路线和洛伐他汀的生物合成途径的国内外研究结果进行了分析比较, 进一步阐述了辛伐他汀生产中可实现生物催化的反应步骤以及用于辛伐他汀直接发酵生产的基因工程菌构建。

Abstract:

Simvastatin, a semisynthetic derivertive of lovastatin, is an important drug for the treatment of hypercholesteromia, and is traditionally prepared by direct alkylation of lovastatin. Chemical reaction conditons are very rigid, and the final product is difficult to purify, also the pressure of labor protection and environment protection is very high. Recently, with the devolpement in the research of lovastatin biosynthesis, more and more attention has been paid to simvastatin biosynthesis. This paper compared the chemical and biological routes in simvastatin production. Simvastatin could be produced by direct fermentation with combinational biosynthesis method, and could also be synthesized from monacolin J with acyltransferase LovD.