Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan; JST-PRESTO, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.
Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan; JST-CREST, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.
Curr Opin Chem Biol. 2018 Oct;46:82-90. doi: 10.1016/j.cbpa.2018.06.014. Epub 2018 Jun 26.
Peptides bearing non-proteinogenic structures characteristic of natural products have great potential as leads of pharmaceuticals. In the biosynthetic pathways of ribosomally synthesized and post-translationally modified peptides (RiPPs), the non-proteinogenic structures are generated by enzymatic structural modification on precursor peptides encoded in genetic information. The plasticity of this pathway, in which alterations of the precursor genes directly resulted in variation of the products by the process of modularly functioning enzymes, have greatly facilitated both in vivo and in vitro engineering of the pathways. Here, we review several examples of the synthesis of artificial peptides having non-proteinogenic structures by genetic engineering of RiPP pathways.
具有天然产物特征的非蛋白结构的肽类具有成为药物先导的巨大潜力。在核糖体合成和翻译后修饰肽（RiPP）的生物合成途径中，非蛋白结构是通过在遗传信息中编码的前体肽上的酶促结构修饰产生的。该途径的可塑性很大，其中前体基因的改变直接通过模块化作用的酶的过程导致产物的变化，这极大地促进了该途径的体内和体外工程化。在这里，我们通过 RiPP 途径的遗传工程，综述了通过遗传工程合成具有非蛋白结构的人工肽的几个例子。
