以分枝杆菌为底盘细胞生物合成甾药中间体的研究进展  

Biosynthesis of steroidal intermediates using Mycobacteria: a review

作　　者：宋士奎 何建新 黄永棋 苏正定 SONG Shikui;HE Jianxin;HUANG Yongqi;SU Zhengding(Department of Biological and Food Engineering,Hubei University of Technology,Wuhan 430068,Hubei,China;Key Laboratory of Industrial Fermentation(Ministry of Education)and Key Laboratory of Industrial Microbiology of Hubei Province,Wuhan 430068,Hubei,China)

机构地区：[1]湖北工业大学生物工程与食品学院,湖北武汉430068 [2]工业发酵教育部重点实验室和湖北省工业微生物重点实验室,湖北武汉430068

出　　处：《生物工程学报》2023年第3期1056-1069,共14页Chinese Journal of Biotechnology

摘　　要：甾体药物(steroid drugs)是一类具有重要生理和药理作用的药物。目前,甾药行业主要通过分枝杆菌(Mycobacteria)转化制备系列重要甾药中间体,再经过必要的化学修饰或酶法修饰获得高端甾体药物。较之前的“薯蓣皂素-双烯醇酮”体系具有原料廉价且来源丰富、生产成本低且反应路线短、收率高且环境友好等优点。基于基因组学和代谢组学进一步揭示分枝杆菌甾醇降解途径中关键酶系及其催化机理,使分枝杆菌作为底盘细胞成为可能。本文对不同物种类固醇转化酶的发现、分枝杆菌自源基因和异源基因过表达的改造以及分枝杆菌作为底盘细胞的优化和修饰等方面的研究进展进行了综述。Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through Mycobacteria transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the “diosgenin-dienolone” route, Mycobacteria transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of Mycobacteria and their catalytic mechanisms are further revealed, which makes it possible for Mycobacteria to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of Mycobacteria genes and the overexpression of heterologous genes, and the optimization and modification of Mycobacteria as chassis cells.

关 键 词：分枝杆菌 底盘细胞 生物转化 甾体药物 

分 类 号：TQ460.1[化学工程—制药化工] TQ426.97