Maruyama Chitose, Hamano Yoshimitsu
Graduate School of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, Japan.
Fukui Bioincubation Center (FBIC), Fukui Prefectural University, Fukui, Japan.
Methods Mol Biol. 2023;2670:3-16. doi: 10.1007/978-1-0716-3214-7_1.
Peptide natural products constitute a major class of secondary metabolites produced by microorganisms (mostly bacteria and fungi). In the past several decades, researchers have gained extensive knowledge about nonribosomal peptides (NRPs) generated by ribosome-independent systems, namely, NRP synthetases (NRPSs). NRPSs are multifunctional enzymes consisting of semiautonomous domains that form a peptide backbone. Using a thiotemplate mechanism that employs assembly-line logic with multiple modules, NRPSs activate, tether, and modify amino acid building blocks, sequentially elongating the peptide chain before releasing the complete peptide. Adenylation, thiolation, condensation, and thioesterase domains play central roles in these reactions. This chapter focuses on the current understanding of these central domains in NRPS assembly-line enzymology.
肽类天然产物是微生物（主要是细菌和真菌）产生的一类主要次级代谢产物。在过去几十年中，研究人员对由非核糖体系统即非核糖体肽合成酶（NRPSs）产生的非核糖体肽（NRPs）有了广泛了解。NRPSs是多功能酶，由形成肽主链的半自主结构域组成。利用采用多模块流水线逻辑的硫酯模板机制，NRPSs激活、连接并修饰氨基酸构建块，在释放完整肽之前依次延长肽链。腺苷化、硫醇化、缩合和硫酯酶结构域在这些反应中起核心作用。本章重点介绍目前对NRPS流水线酶学中这些核心结构域的理解。
