酿酒酵母中胆固醇生物合成与优化的研究进展

Biosynthesis and optimization of cholesterol in Saccharomyces cerevisiae

胆固醇是动物体内积累的主要甾醇化合物,在维持细胞膜功能、合成甾体激素、生产甾体药物中间体等方面具有重要的生物学意义和医学应用价值。传统动物组织提取胆固醇的方法费时费力并存在严重的环境污染问题,而甾醇分子结构的复杂程度也限制了其化学全合成。近些年,人们利用合成生物学方法构建的微生物细胞工厂已成功用于萜类、甾醇类等天然产物的开发与合成。文中综述了胆固醇微生物细胞工厂的研究进展,包括胆固醇生物合成途径的解析、底盘菌株的选择、异源基因元件的挖掘与优化、相关代谢通路的调控等方面,并讨论了当前研究面临的问题,以期为胆固醇的高效生物合成提供参考。

Cholesterol is a major sterol compounds accumulating in animals,which has important biological significance and medical application value in maintaining cell membrane function,synthesizing steroid hormones,and producing steroid drug intermediates.Traditionally,cholesterol is obtained by animal tissue extraction,but the whole process is time-consuming and laborious,accompanied by severe environmental pollution.Due to the complex and delicate structure,steroids are difficult to be produced by chemical total synthesis.Most recently,microbial cell factories constructed by synthetic biology have been successfully applied on the biosynthesis and development of natural products,such as terpenoids and sterols.This paper summarized the research progress on cholesterol microbial cell factories,including characterization of cholesterol biosynthesis pathway,selection of chassis strains,mining and optimization of heterologous gene components,and regulation of metabolic pathway,as well as discussed the problems faced by the current research,hoping to provide references for the effective biosynthesis of cholesterol.