中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
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《生命科学》 2013, 25(10): 958-965
合成生物技术生产甾体激素中间体的研究展望
刘 夺,张 莹,周 晓*,元英进
(天津大学化工学院系统生物工程教育部重点实验室,天津 300072)
摘 要:甾体类药物是销售额仅次于抗生素的世界第二大类药物,不同的甾体药物分子结构均由甾体激素中间体衍生而来。甾体激素中间体的传统生产方法包括植物提取皂素法和化学全合成法,其对环境有害,反应产物结构不唯一且成本较高,不利于工业化生产。目前主要的生产工艺是利用微生物对特殊原料进行转化的半合成法,但会遇到微生物酶转化率低、发酵周期长等问题。合成生物学的出现为构建利用糖为唯一碳源生产甾体激素中间体的人工细胞提供了理论上的可行性和可靠的技术支持。重点综述了合成生物技术在甾体激素中间体生产中的应用,以有利于工业发酵的酿酒酵母、分枝杆菌等为底盘细胞,通过引入外源合成功能模块,实现胆甾醇、雄烯二酮等甾体激素中间体的生物合成,并对合成生物技术在医药生产方式转变中的应用进行了展望,以期推动甾体类药物生物制造技术的进步。
 
Research prospects of synthetic biotechnology in steroid hormone intermediate production
    
LIU Duo, ZHANG Ying, ZHOU Xiao*, YUAN Ying-Jin
(Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China)
Abstract: Steroid drugs have become the second one in the world pharmaceutical market, right after the antibiotics. All types of steroid drugs are derived from the steroid hormone intermediates. For the production of steroid hormone intermediates, traditional methods include plant saponin extraction method and total synthesis method. Both of them are detrimental to environment, yield the mixing of different structural products, and too expensive for industrial production. At present, the common method is semi-synthesis which uses certain raw material and microorganisms, while faces the problems such as low enzyme conversion rate and long fermentation period. The advent of synthetic biology provides a theoretical basis and reliable technical support for constructing artificial cells that can synthesize steroid hormone intermediates using sugar as the sole carbon resource. This review summarized the application of synthetic biotechnology in the production of steroid hormone intermediates. Cholesterol,
    androstendione and other steroid intermediates can be synthesized by introducing exogenous synthetic function modules, using Saccharomyces cerevisiae and mycobacteria as chassis suitable for industrial fermentation. Furthermore, the application of synthetic biotechnology is also discussed in changing pharmaceutical production mode, expecting to promote the progress of steroid biological pharmaceutical technologies.
 
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