基于生物合成的双环硫肽类抗生素结构改造进展  

Progress in Structural Modification of Bicyclic Thiopeptide Antibiotics Based on Biosynthesis

作　　者：张鄂 陈单丹[2] 王守锋 刘文[2,3] Zhang E;Chen Dandan;Wang Shoufeng;Liu Wen(Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials,School of Chemistry and Chemical Engineering,University of Jinan,Jinan 250022;State Key Laboratory of Bioorganic and Natural Products Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032;Huzhou Center of Bio-Synthetic Innovation,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Huzhou,Zhejiang 313000)

机构地区：[1]济南大学化学化工学院,山东省氟化学化工材料重点实验室,济南250022 [2]中国科学院上海有机化学研究所生命有机化学国家重点实验室,上海200032 [3]中国科学院上海有机化学研究所,湖州生物制造中心,浙江湖州313000

出　　处：《有机化学》2020年第10期3120-3131,共12页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.31972850,21750004,21520102004);山东省重点研发计划(No.2019GSF108223);中国科学院(Nos.QYZDJ-SSW-SLH037,XDB20020200);上海市科委(No.17JC1405100);中国科学院青年创新促进会(No.2017303);王宽诚教育基金会资助项目.

摘　　要：硫肽类抗生素是一类由微生物次级代谢产生的富含硫元素且结构被高度修饰的聚噻(噁)唑多肽类天然产物,具有良好的生物活性.由于水溶性差以及生物利用度低等问题,导致该类抗生素在临床上的应用受到限制.在了解其生物合成机制的基础上,通过合理的生物工程改造来获得硫肽类似物的方法成了生物学家们关注的焦点.以双环硫肽家族中的硫链丝菌素和那西肽为代表,综述了双环硫肽类抗生素结构改造的进展.Thiopeptide antibiotics are a class of natural products with polythiophene(oxazol)polypeptides,which are rich in sulfur and highly modified.They are produced by secondary metabolism of microorganisms and have good biological activities.Developing thiopeptides into clinic is currently a challenge partly due to their low aqueous solubility and associated poor bioavailability.On the basis of understanding the mechanism of their biosynthesis,the method of obtaining thiopeptide analogues via reasonable bioengineering has become the research focus of biologists.In this paper,the advances in structural modifications of bicyclic thiopeptides by taking thiostrepton and nosiheptide as representatives are reviewed.

关 键 词：生物合成 硫链丝菌素 那西肽 结构改造 

分 类 号：R978.1[医药卫生—药品]