鬼臼毒素的生物合成及药理活性研究进展  

Research Progress on Biosynthesis and Pharmacological Activity of Podophyllotoxin

作　　者：蒲香谷 江丽洁 陈籽亦 刘巨钊 崔琦 PU Xianggu;JIANG Lijie;CHEN Ziyi;LIU Juzhao;CUI Qi(Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学,杭州310053

出　　处：《中国现代应用药学》2024年第11期1557-1567,共11页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(82204552);中国博士后科学基金项目(2021M692893,2021M702927);浙江省自然科学基金项目(LQ24H280009);浙江省中医药科技计划项目(2023ZR087)。

摘　　要：鬼臼毒素是来源于鬼臼属植物的芳基萘类木脂素化合物,是鬼臼属植物的次级代谢产物,同时也是植物来源的药用天然产物,具有广谱抗肿瘤活性,目前对鬼臼毒素的相关研究较少。中国是鬼臼属植物的多样性中心和分布中心,为保护其现有资源,鬼臼毒素的生物合成特别是合成生物学研究逐渐成为当今研究的新方向。鬼臼毒素及其类似物具有强烈细胞毒性,对多种肿瘤细胞、病毒、细菌的增殖均有良好的抑制效果,广泛应用于各类肿瘤的临床治疗。本文对鬼臼属植物在中国的植物分布进行归纳总结,对鬼臼毒素的生物合成步骤、应用及生物学研究进行综述,同时概述了鬼臼毒素的药理活性,以期为鬼臼资源的应用、鬼臼毒素的合成、鬼臼类药物的开发提供参考。Podophyllotoxin is an aryl naphthalene lignan-like secondary metabolite,which is widely existed in plants of the Podophyllum.It exhibits a broad spectrum of antitumor activity and holds significant clinical value as a medicinal natural product of plant origin.This review discusses podophyllotoxin from three aspects:plant distribution,biosynthesis and pharmacological effects.Distribution of podophyllotoxin in nature:Podophyllotoxin and its analogues are mainly found in 12 genera of three families,which are Berberidaceae,Linaceae and Cupressaceae,respectively.They are mostly distributed in East Asia and North America,especially in China,which is not only the diversity center of the Podophyllum,but also the distribution center.Among all these plants,the genera Dysosma and Sinopodophyllum are the focus of the relevant research.Biosynthesis of podophyllotoxin:In order to take the alleviation of the pressure of podophyllotoxin that is in short supply of natural resources,and to protect its existing resources,the biosynthesis of podophyllotoxin,especially synthetic biology,has gradually become a new direction of current research.Compared with chemical synthesis which has the shortcoming of low synthesis efficiency,high production cost and cumbersome steps,biosynthesis has a variety of advantages.It’s not limited by resources,easy to cultivate on a large scale and has fast production speed,low production cost and simple genetic manipulation,so there is a broader prospect for the exact purpose of biosynthetic development.The biosynthesis of podophyllotoxin is divided into four steps in general,including the synthesis of coniferyl alcohol,the synthesis of matairesinol,the synthesis of deoxypodophyllotoxin and the synthesis of podophyllotoxin.It requires various enzymes catalyzed during the synthesis process,such as pinoresinol-lariciresinol reductase(PLR),secoisolariciresinol dehydrogenase(SDH)and others.At present,by means of synthetic biology,heterologous production of natural drugs in microbial cell factories,the synt

关 键 词：鬼臼毒素 鬼臼属植物 生物合成 抗肿瘤 

分 类 号：R914.4[医药卫生—药物化学]