Chakravarti R, Sahai V
Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology-Delhi, Hauz Khas, 110016, New Delhi, India.
Appl Microbiol Biotechnol. 2004 Jun;64(5):618-24. doi: 10.1007/s00253-003-1553-7. Epub 2004 Mar 19.
Compactin, a hypocholesterolemic molecule, is a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, which is a regulatory enzyme for cholesterol biosynthesis. The structural similarity and high affinity of the acid form of compactin and HMG, the natural substrate of enzyme, results in specific and effective inhibition of this enzyme. Inhibition results in reduced levels of mevalonic acid in the body, leading to pleiotropic effects. Various fungi have been used for the commercial production of compactin. Using different strategies for improving production levels, yields have been increased to around 900 times of the amount originally produced. Recently, the gene sequence responsible for compactin production has been cloned and sequenced. This review deals with the chemistry, mode of action, pharmacology, biosynthesis, and production of compactin. A comparative study of various reports dealing with the production of compactin is also included.
美伐他汀是一种降胆固醇分子，是3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的竞争性抑制剂，该还原酶是胆固醇生物合成的调节酶。美伐他汀的酸形式与该酶的天然底物HMG在结构上相似且亲和力高，导致对该酶产生特异性且有效的抑制作用。抑制作用会使体内甲羟戊酸水平降低，从而产生多种效应。各种真菌已被用于美伐他汀的商业生产。通过采用不同的策略提高生产水平，产量已提高到原来产量的约900倍。最近，负责美伐他汀生产的基因序列已被克隆和测序。本文综述了美伐他汀的化学、作用方式、药理学、生物合成及生产。还包括对有关美伐他汀生产的各种报告的比较研究。
