Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, 710069, China.
Department of Scientific Research and Development, Tsinghua University, Beijing, 100084, China.
Bioprocess Biosyst Eng. 2019 Sep;42(9):1537-1545. doi: 10.1007/s00449-019-02151-4. Epub 2019 Jun 1.
7α- and 7β-hydroxysteroid dehydrogenases (HSDHs) are key biocatalysts for the biotransformation of ursodeoxycholic acid (UDCA) from chenodeoxycholic acid (CDCA). Various researches focused on heterogeneously expressed engineering enzymes to epimerize CDCA for UDCA, however not yet applied to further industrial application. In this work, we present the large-scale production of UDCA from CDCA by 7α- and 7β-HSDH enzymatic synthesis. Engineering enzymes were both successfully heterologous overexpressed in Escherichia coli BL21, and the effect of the enzymatic synthesis was investigated. The mass analysis (MS), IR spectrum, H NMR and C NMR were used to characterize the product. 500-L fermentor fermentation strategy producing a stable supply of HSDH and large-scale production process of UDCA in dozens kilogram class enabled industrial application.
7α-和 7β-羟甾脱氢酶（HSDHs）是将熊去氧胆酸（UDCA）从鹅去氧胆酸（CDCA）生物转化为关键的生物催化剂。各种研究都集中在异源表达工程酶以将 CDCA 表异构化为 UDCA 上，但尚未应用于进一步的工业应用。在这项工作中，我们通过 7α-和 7β-HSDH 酶促合成展示了从 CDCA 大规模生产 UDCA。工程酶均在大肠杆菌 BL21 中成功异源过表达，并对酶促合成的效果进行了研究。采用质量分析（MS）、红外光谱（IR）、H NMR 和 C NMR 对产物进行了表征。500-L 发酵罐发酵策略可稳定供应 HSDH，并可进行数十公斤级的 UDCA 大规模生产工艺，从而实现了工业化应用。
