Greenspan M D, Yudkovitz J B
J Bacteriol. 1985 May;162(2):704-7. doi: 10.1128/jb.162.2.704-707.1985.
Mevinolinic acid, the open acid form of mevinolin, which is a metabolite of Aspergillus terreus, has been shown to be a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (Alberts et al., Proc. Natl. Acad. Sci. U.S.A. 77:3957-3961, 1980). The biosynthesis of mevinolinic acid was studied by examining the incorporation of [1-14C]acetate and [methyl-14C]methionine into the molecule. These isotopes were rapidly incorporated into mevinolinic acid, with [1-14C]acetate and [methyl-14C]methionine incorporation being linear for at least 10 and 30 min, respectively. A comparison of acetate incorporation into mevinolinic acid and fatty acids indicated that mevinolinic acid biosynthesis increased with a maximum between days 3 and 5 of growth; at this time cell growth had ceased and fatty acid biosynthesis was negligible. Hydrolysis of the mevinolinic acid and isolation of the products showed that [1-14C]acetate and [methyl-14C]methionine were incorporated into the 2-methylbutyric acid side chain as well as into the main (alcohol) portion of the molecule.
美伐他汀酸是美伐他汀的开环酸形式，它是土曲霉的一种代谢产物，已被证明是3-羟基-3-甲基戊二酰辅酶A还原酶的竞争性抑制剂（阿尔伯茨等人，《美国国家科学院院刊》77:3957 - 3961，1980年）。通过检测[1-¹⁴C]乙酸盐和[甲基-¹⁴C]甲硫氨酸掺入该分子的情况，对美伐他汀酸的生物合成进行了研究。这些同位素迅速掺入美伐他汀酸中，[1-¹⁴C]乙酸盐和[甲基-¹⁴C]甲硫氨酸的掺入分别至少在10分钟和30分钟内呈线性。将乙酸盐掺入美伐他汀酸和脂肪酸的情况进行比较表明，美伐他汀酸的生物合成在生长的第3天至第5天之间增加到最大值；此时细胞生长已经停止，脂肪酸的生物合成可以忽略不计。美伐他汀酸的水解及产物的分离表明，[1-¹⁴C]乙酸盐和[甲基-¹⁴C]甲硫氨酸既掺入了2-甲基丁酸侧链，也掺入了分子的主要（醇）部分。
