熊去氧胆酸还原酶稳定性研究进展
摘要：熊去氧胆酸是一种亲水性胆汁酸(UDCA)，是治疗肝胆疾病的重要药物之一。以鹅去氧胆酸为原料酶法合成熊去氧胆酸涉及到两种酶，其中的熊去氧胆酸还原酶--7beta;-羟基类固醇脱氢酶（7beta;-HSDH），在因受到反应中的产物浓度的抑制而不稳定，这严重影响了熊去氧胆酸生物合成的效率。近年来，研究者们通过工艺优化、发掘新酶和酶分子改造， 在7beta;-HSDH的稳定性提高方面取得了一定进展。本文对熊去氧胆酸还原酶稳定性进展进行了综述，分析并展望未来发展方向。
关键词 熊去氧胆酸 7beta;-羟基类固醇脱氢酶 生物合成法 分子改造
Research progress on the stability of ursodeoxycholate reductase
Abstract: Ursodeoxycholic acid is a hydrophilic bile acid (UDCA), which is one of the important drugs for the treatment of hepatobiliary diseases. The enzymatic synthesis of ursodeoxycholic acid from chenodeoxycholic acid involves two enzymes. Among them, ursodeoxycholate reductase, 7beta;-hydroxysteroid dehydrogenase (7beta;-HSDH), is unstable due to the inhibition of the concentration of the product in the reaction, which seriously affects the efficiency of ursodeoxycholic acid biosynthesis. In recent years, researchers have made some progress in improving the stability of 7beta;-HSDH through process optimization, discovery of new enzymes and modification of enzyme molecules. This paper reviews the progress in the stability of ursodeoxycholate reductase, analyzes and looks forward to the future development direction.
Key words: ursodeoxycholic acid; 7beta;-hydroxysteroid ;Biosynthesis method; Molecular modification
1.引言
熊去氧胆酸( ursodeoxycholic acid， UDCA， 图 1) 是一种具有多种生物活性的亲水性胆汁酸，又名 3alpha;， 7beta;-二羟基-5beta;-胆甾烷-24-酸， 在化学结构上是由 3 个六元环、1 个五元环组成的甾体骨架和 1个脂肪侧链共 24 个碳原子构成的甾体化合物[1]。
