加拿大麦吉尔大学Martin Schmeing及其团队利用双模块非核糖体肽合成酶的结构揭示了其构象灵活性。2019年11月8日，《科学》发表了这一研究成果。

研究人员确定了非核糖体肽合成酶（NRPS）线性短杆菌肽合成酶的大型构建体的五个X射线晶体结构，包括以缩合反应和模块间肽基底物传递形式组织的全核心双模块结构。该结构揭示了相邻模块相对位置的差异，而这些差异并非严格地与催化循环相关，并且与小角度X射线散射数据一致。同源物的结构和共变分析使研究人员能够创建突变体，从而提高模块交换双模块NRPS的多肽产量。

据介绍，NRPS是利用模块合成逻辑合成天然产物治疗剂的生物合成酶，其中每个模块都会向新生肽中添加一个氨酰基底物。

附：英文原文

Title: Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility

Author: Janice M. Reimer, Maximilian Eivaskhani, Ingrid Harb, Alba Guarné, Martin Weigt, T. Martin Schmeing

Issue&Volume: Volume 366 Issue 6466

Abstract: Nonribosomal peptide synthetases (NRPSs) are biosynthetic enzymes that synthesize natural product therapeutics using a modular synthetic logic, whereby each module adds one aminoacyl substrate to the nascent peptide. We have determined five x-ray crystal structures of large constructs of the NRPS linear gramicidin synthetase, including a structure of a full core dimodule in conformations organized for the condensation reaction and intermodular peptidyl substrate delivery. The structures reveal differences in the relative positions of adjacent modules, which are not strictly coupled to the catalytic cycle and are consistent with small-angle x-ray scattering data. The structures and covariation analysis of homologs allowed us to create mutants that improve the yield of a peptide from a module-swapped dimodular NRPS.

DOI: 10.1126/science.aaw4388

Source: https://science.sciencemag.org/content/366/6466/eaaw4388