非核糖体肽合成酶(NRPSs)作用机理与应用的研究进展

Advances in the study of the mechanism and application of nonribosomal peptide synthetases

摘要:

许多微生物能利用非核糖体肽合成酶(NRPSs)合成结构复杂、种类繁多的的生物活性肽。非核糖体肽因其独特的理化特性和药理学特性已被广泛关注,极具商业开发潜力。NRPSs由多个模块组成,模块的不同空间排列顺序决定其多肽产物的氨基酸序列特异性。NRPSs以多载体巯基化模板机理进行多肽合成,其底物特异性由腺苷酰化结构域和缩合结构域共同实现。目前,人们已经利用天然的NRPSs、某些特定结构域、将已知NRPSs的模块或特定结构域进行组合甚至杂合组合而构建成的新的NRPSs来合成目的多肽。

Abstract:

Many microorganisms could use nonribosomal peptide synthetases (NRPSs) to synthesize various bioactive peptides with complicated structures. Because of their special physical-chemical and pharmacological properties, the nonribosomal peptides (NRPs) had been extensively studied, and would have great potential for commercial application. NRPSs are composed of many iterative modules whose different assembling orders determine the specificity of amino acid sequences of their peptide products. The NRPs are assembled by NRPSs via multiple-carrier thiotemplate mechanism, and the substrate specificity of NRPSs is determined by both adenylation domain and condensation domain. Recently, many expected peptides were synthesized using natural whole NRPSs, some specific domains of NRPSs, or novel NRPSs which were constructed by the combination or hybrid combination of specific modules or domains of some known NRPSs.