State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, Shanghai, 200237, China.
Chembiochem. 2018 Feb 16;19(4):347-353. doi: 10.1002/cbic.201700415. Epub 2017 Oct 24.
Ursodeoxycholic acid (UDCA) is an effective drug for the treatment of hepatitis. In this study, 7α-hydroxysteroid dehydrogenase (7α-HSDH) and lactate dehydrogenase (LDH), as well as 7β-hydroxysteroid dehydrogenase (7β-HSDH) and glucose dehydrogenase (GDH), were co-immobilized onto an epoxy-functionalized resin (ES-103) to catalyze the synthesis of UDCA from chenodeoxycholic acid (CDCA). Through optimizing the immobilization pH, time, and loading ratio of enzymes to resin, the specific activities of immobilized LDH-7αHSDH@ES-103 and 7βHSDH-GDH@ES-103 were 43.2 and 25.8 U g , respectively, which were 12- and 516-fold higher than that under the initial immobilization conditions. Continuous production of UDCA from CDCA was subsequently achieved by using immobilized LDH-7αHSDH@ES-103 and 7βHSDH-GDH@ES-103 in two serial packed-bed reactors. The yield of UDCA reached nearly 100 % and lasted for at least 12 h in the packed-bed reactors, which was superior to that of the batchwise reaction. This efficient continuous approach developed herein might provide a feasible route for large-scale biotransformation of CDCA into UDCA.
熊去氧胆酸（UDCA）是治疗肝炎的有效药物。在这项研究中，7α-羟甾脱氢酶（7α-HSDH）和乳酸脱氢酶（LDH），以及 7β-羟甾脱氢酶（7β-HSDH）和葡萄糖脱氢酶（GDH）被共固定到环氧功能化树脂（ES-103）上，以催化从鹅去氧胆酸（CDCA）合成 UDCA。通过优化固定化 pH 值、时间和酶与树脂的负载比，固定化 LDH-7αHSDH@ES-103 和 7βHSDH-GDH@ES-103 的比活性分别为 43.2 和 25.8 U/g，分别比初始固定化条件下提高了 12 倍和 516 倍。随后，使用固定化 LDH-7αHSDH@ES-103 和 7βHSDH-GDH@ES-103 在两个串联的填充床反应器中连续生产 CDCA 生成 UDCA。在填充床反应器中，UDCA 的产率接近 100%，至少持续 12 h，优于分批反应。本文开发的这种高效连续方法可能为 CDCA 大规模生物转化为 UDCA 提供了一种可行的途径。
