School of Biological Sciences, Victoria University of Wellington, New Zealand.
Nat Prod Rep. 2018 Nov 14;35(11):1210-1228. doi: 10.1039/c8np00036k.
Covering: up to May 2018 Non-ribosomal peptide synthetases (NRPSs) are mega-enzymes that form modular templates to assemble specific peptide products, independent of the ribosome. The autonomous nature of the modules in the template offers prospects for re-engineering NRPS enzymes to generate modified peptide products. Although this has clearly been a primary mechanism of natural product diversification throughout evolution, equivalent strategies have proven challenging to implement in the laboratory. In this review we examine key examples of successful and less-successful re-engineering of NRPS templates to generate novel peptides, with the aim of extracting practical guidelines to inform future efforts. We emphasise the importance of maintaining effective protein-protein interactions in recombinant NRPS templates, and identify strengths and limitations of diverse strategies for achieving different engineering outcomes.
截至 2018 年 5 月 非核糖体肽合成酶（NRPSs）是形成模块化模板以组装特定肽产物的巨型酶，独立于核糖体。模板中模块的自主性质为改造 NRPS 酶以产生修饰肽产物提供了前景。尽管这显然是整个进化过程中天然产物多样化的主要机制，但在实验室中实施等效策略已被证明具有挑战性。在这篇综述中，我们检查了成功和不太成功的 NRPS 模板改造的关键实例，以生成新型肽，旨在提取实用的指导原则，为未来的努力提供信息。我们强调了在重组 NRPS 模板中保持有效蛋白质-蛋白质相互作用的重要性，并确定了实现不同工程结果的各种策略的优缺点。
