摘要
熊去氧胆酸(UDCA)是治疗肝胆疾病的基础性药物,对某些癌症和神经系统疾病也有辅助治疗作用。化学工艺合成UDCA对环境不友好、收率低,尚不能满足生产需求;生物法合成UDCA具有转化率高、节省能源、对环境友好的特点,目前是UDCA合成的研究发展方向。生物法合成是以廉价易得的鹅去氧胆酸(CDCA)、胆酸(CA)或石胆酸(LCA)为底物,通过7α-HSDH、7β-HSDH、LDH和GDH四种酶催化合成UDCA,合成方法分为游离酶催化和全细胞合成,其中游离酶催化常采用“一锅两步法”或“一锅一步法”合成UDCA;全细胞催化是以构建的工程细胞作为反应容器,利用细胞表达的酶系催化合成UDCA。本文综述了游离酶催化和全细胞合成UDCA的相关用酶、合成方式及合成工艺的研究进展,为UDCA的研究生产提供技术参考。
Ursodeoxycholic acid(UDCA)is a fundamental medication in the treatment of hepatobiliary diseases and used as an adjuvant in the treatment of certain cancers and neurological disorders.The chemical synthesis method of UDCA is environmentally unfriendly,low yields output and cannot be fully met the production demand yet.In contrast,the biosynthesis of UDCA is characterized by high conversion rates,low energy conservation,and environmental friendliness.At present,it represent the direction of research and development for UDCA synthesis.Availabled substrates are utilized for biosynthesis such as chenodeoxycholic acid(CDCA),cholic acid(CA),or lithocholic acid(LCA).substrates are catalyzed by four enzymes:7alpha-hydroxysteroid dehydrogenase(7α-HSDH),7beta-hydroxysteroid dehydrogenase(7β-HSDH),Lactate dehydrogenase(LDH),and Glucose dehydrogenase(GDH).There are two methods for synthesizing UDCA.It includes free enzyme catalysis and whole-cell synthesis.Free enzyme catalysis method are subdivided into“one-pot two-step”and“one-pot one-step”.Whole-cell catalysis uses engineered cells as reaction vessels.The synthesis of UDCA is catalyzed by enzyme systems of cell.This paper reviews This article gives an overview of the enzymes involved,synthesis methods and the progress in synthesis technology for both free enzyme catalysis and whole-cell synthesis of UDCA.It provides technical references for the research and production of UDCA.
作者
张雪
张悦
刘梦雨
栾浩妮
宋鹏
周正松
王飞
徐伟
ZHANG Xue;ZHANG Yue;LIU Mengyu;LUAN Haoni;SONG Peng;ZHOU Zhengsong;WANG Fei;XU Wei(School of Life Sciences,Liaocheng University,Liaocheng 252059,China;Shandong Aokete Biotechnology Co.Ltd.,Liaocheng 252800,China)
出处
《聊城大学学报（自然科学版）》
2024年第2期101-110,共10页
Journal of Liaocheng University:Natural Science Edition
基金
国家自然科学基金青年项目(82304838)
山东省自然科学基金面上项目(ZR2022MC159)资助。
关键词
熊去氧胆酸
生物法合成
游离酶催化合成
全细胞合成
ursodeoxycholic acid
biological synthesis
free enzyme-catalyzed synthesis
whole-cell synthesis
