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

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.