免疫抑制剂他克莫司生物合成的研究进展

Biosynthesis of immunosuppressant tacrolimus:a review

他克莫司(FK506)是一种具有免疫抑制活性的23元大环内酯类化合物,临床上广泛用于防止器官移植术后的免疫排斥反应。生物合成法是他克莫司制备方法的研究热点,但他克莫司生物合成的研究还存在一定生产技术上的瓶颈。基于此,本文主要从他克莫司代谢途径改造和发酵过程控制等方面对他克莫司生物合成进展进行综述,以期为今后突破他克莫司生物合成的技术瓶颈提供参考,进而利用代谢工程、发酵工程等技术提升他克莫司的生物合成水平。

Tacrolimus(FK506)is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation.The research on tacrolimus production was mainly focused on biosynthesis methods,within which there are still some bottlenecks.This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process,with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.