组合生物学技术合成他克莫司类似物的研究进展

Biosynthesis of FK506 analogs by combinatorial biological techniques

摘要:

近年来组合生物学技术在开发抗生素类似物的研究中发挥着越来越重要的作用，在他克莫司类似物的组合生物合成中，通过应用外源合成前体取代烯丙基丙二酸单酰基和4,5-二羟基-1-烯-环己甲酸，以及应用模块化合成元件取代AM合成元件和改造后修饰合成元件，已经生产出11个他克莫司类似物，这些研究拓宽了人们对标准化合成前体和模块化合成元件的认识，为通过组合生物合成手段进行抗生素的更新换代提供指导。

关键词:他克莫司，合成前体，合成元件，合成途径

Abstract:

More and more antibiotic analogs are biosynthesized by combinatorial biological techniques. Eleven FK506 analogs are biosynthesized through replacement of allylmalonyl group and 4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid group with heterologous building blocks, and replacement of allylmalonyl biosynthetic elements with heterologous modular biosynthetic elements. These studies will expand our understanding of heterologous building blocks and modular biosynthetic elements and may help us generate more new antibiotic analogs.

Key words:FK506, Building block, Biosynthetic element, Biosynthetic pathway