Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA.
J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):493-513. doi: 10.1007/s10295-018-02130-w. Epub 2019 Jan 23.
Nonribosomal peptide synthetases (NRPSs) are involved in the biosynthesis of numerous peptide and peptide-like natural products that have been exploited in medicine, agriculture, and biotechnology, among other fields. As a consequence, there have been considerable efforts aimed at understanding how NRPSs orchestrate the assembly of these natural products. This review highlights several recent examples that continue to expand upon the fundamental knowledge of NRPS mechanism and includes (1) the discovery of new NRPS substrates and the mechanism by which these sometimes structurally complex substrates are made, (2) the characterization of new NRPS activities and domains that function during the process of peptide assembly, and (3) the various catalytic strategies that are utilized to release the NRPS product. These findings continue to strengthen the predictive power for connecting genes to products, thereby facilitating natural product discovery and development in the Genomics Era.
非核糖体肽合成酶（NRPSs）参与了许多肽和肽样天然产物的生物合成，这些产物在医学、农业和生物技术等领域得到了广泛应用。因此，人们做出了相当大的努力来理解 NRPSs 如何协调这些天然产物的组装。这篇综述强调了几个最近的例子，这些例子继续扩展了 NRPS 机制的基本知识，包括：（1）发现新的 NRPS 底物以及这些结构复杂的底物的产生机制；（2）新的 NRPS 活性和结构域的特征，这些结构域在肽组装过程中发挥作用；（3）用于释放 NRPS 产物的各种催化策略。这些发现继续增强了将基因与产物联系起来的预测能力，从而促进了基因组时代的天然产物发现和开发。
