蟾蜍二烯酸内酯类成分的生物转化和生物合成研究进展

Research progress on biotransformation and biosynthesis of bufadienolides

蟾蜍二烯酸内酯类化合物是名贵中药蟾酥的主要活性成分,具有显著的抗肿瘤、强心、镇痛和抗炎等药理活性。目前,蟾蜍二烯酸内酯成分的主要来源方法是从蟾蜍类药材中直接提取,但此方法成本高、收益低,且药用资源十分短缺,相关新药开发与应用研究严重受阻。近年来,中药活性成分的生物合成在中药资源保护方面发挥起越来越重要的作用。基于合成生物学原理,设计和改造微生物菌株发酵生产天然产物的方法已被广泛使用。该方法的应用需要建立在目标产物生物合成途径完全解析的基础之上。基于此,总结近年来蟾蜍二烯酸内酯的生物转化以及生物合成途径解析方面的研究进展,并进一步推测蟾蜍二烯酸内酯类的生物合成途径,并进一步展望与其相关的生物合成发展方向。

Bufadienolides are the main active ingredients of traditional Chinese medicine(TCM)Chansu(Bufonis Venenum)that have significant pharmacological activities such as antitumor,cardiac,analgesic and anti-inflammatory.Until now,the acquisition of bufadienolides is still mainly extracted from toad medicinal materials.However,the cost of this method is high and the profit is quite low.Meanwhile,the medicinal resources of bufadienolides are deficient seriously.Hence,the associated drug development and usage was greatly limited.In recent years,researches on the synthetic biology of active ingredients of TCM have played an increasingly important role in protecting the resources of TCM.Based on the principles of synthetic biology,the method of designing and modifying microbial strains to produce natural products has been widely applied.Yet,the application of this method should be based on the elucidation of biosynthetic pathways of target compounds.This review summarized the recent research progresses on the biotransformation and biosynthesis of bufadienolides.Furthermore,the biosynthetic pathways of bufadienolides were speculated and related future directions for producing these compounds have been prospected as well.