非核糖体肽合成酶体系设计和改造研究进展

Advances in design and modification of non-ribosomal peptide synthetase system

自然界中,微生物合成肽类化合物一般通过核糖体途径合成核糖体肽,而非核糖体肽(nonribosomal peptide,NP)是一类不通过核糖体途径、由非核糖体肽合成酶(nonribosomal peptide synthetase,NRPS)催化合成的肽类化合物。非核糖体肽合成酶是一种模块化、线性化组装的酶,以类似流水装配线的方式发挥作用。它们产生的次生代谢物多肽通常具有非常复杂的结构,其中有许多是具有重要药理意义的天然产物。NRPS的模块化性质导致其可以通过模块重组实现产物多样化,基于这个发现,科学家们对其进行了深入研究,以期通过人为改造和重构等方式产生更多更有价值的产物。该文集中介绍近年来通过NRPS人工改造和重组等方式生产多肽的研究,为未来发现和生产新的生物活性化合物提供思路。

In nature,peptides are synthesized mainly by microorganisms through the ribosomal pathway,but non-ribosomal peptides(NP)are a special kind of peptide synthesized by non-ribosomal peptide synthase(NRPS)pathway.NRPS is a modular,linearized assembled enzyme that functions like a manner similar to an assembly line.The secondary metabolite peptides produced by NRPS usually have very complex structures,and many of which are natural products with crucial pharmacological significance.Based on the finding that NRPS can diversify its products through module recombination due to its modularity,scientists have conducted in-depth researches on it in order to produce more valuable products through module splicing and reconstruction.This review focuses on the development on the production of NPs by reconstruction and engineering of NRPS in recent years,providing ideas for the discovery and production of new bioactive compounds in the future.