拟无枝酸菌ST2710转化洛伐他汀为无锡他汀的初步研究  

The Studying of Transformation Process in Amycolatopsis sp.Cell Converting Lovastatin into Wuxistatin

作　　者：付维来[1] 诸葛斌[1] 于海[1] 方慧英[1] 诸葛健[1] 

机构地区：[1]江南大学工业生物技术教育部重点实验室和工业微生物研究中心,江苏无锡214122

出　　处：《食品与发酵工业》2009年第10期23-27,共5页Food and Fermentation Industries

基　　金：江南大学自然预研基金资助(2008LYY017)

摘　　要：无锡他汀是新发现的胆固醇合成途径中限速酶羟甲基戊二酰辅酶A(HMG-CoA)还原酶的抑制剂,对HMG-CoA还原酶的抑制作用是洛伐他汀的4倍,是一种非常具有开发潜力的高效降脂新药。研究发现,转化过程中,伴随无锡他汀的形成,存在着另一种转化化合物Ⅰ。通过液质联用和核磁共振测定及对所获图谱进行解析,获得产物Ⅰ的分子结构为2-甲基丁酸-1,2,3,7,8,8a-六氢-3-羟甲基-7-二甲基-8-[2-[(2R,4R-4-羟基-6氧代-2-四氢吡喃基]-乙基]-1-萘酯,与无锡他汀是同分异构体。同时发现产物Ⅰ的形成对无锡他汀的形成存在一定的影响,这一发现为如何提高无锡他汀转化提供了理论基础。Wuxistatin is a novel inhibitor of 3-hydroxy-3-methylglutary（HMG-CoA） reductase which is the rate- limiting enzyme in the process of eholesterol synthesis. Its inhibitory effect of the reduetase is four times more efficient than that of Lovastatin, thus it is a new potential drug for reducing the level of cholesterol. With the production of wuxistatin, aeeording to our research, there is another eompound named biotransformating produet Ⅰ. Through NMR and LC-MS analysis, moleeular structure of biotransformating product Ⅰ is 2-methyl-, 1,2,3,7,8,8a- hexahydro-3- （ hydroxymethyl ） -7-methyl-8-[ 2-（ tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl ） ethy] -1 -naphthalenyl ester. Bio transformating product Ⅰ and wuxistatin are isomers. In addition, the formation of product 1 will influenee the formation and existence of wuxistain to some extent, which provides theoretieal basis for increasing the production of wuxistatin.

关 键 词：无锡他汀 核磁共振 液质联用 同分异构体 

分 类 号：TQ460.1[化学工程—制药化工]