State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
Org Biomol Chem. 2020 Aug 12;18(31):6095-6099. doi: 10.1039/d0ob01215g.
NAI-112 is a glycosylated class III lanthipeptide produced by an Actinoplanes sp. strain with potent bioactivity against nociceptive pain. It contains two labionin/methyllabionin motifs and a rare deoxyhexose modification N-linked to a tryptophan residue. In this study, we investigated the substrate tolerance of the biosynthetic machinery of NAI-112 by using a heterologous co-expression system in Escherichia coli. The results demonstrate AplKC as the first class III lanthipeptide synthetase to catalyze the formation of two labionin/methyllabionin motifs independently. As a rare Trp(N) glycosyltransferase, AplG shows the requirement of two intact ring structures in peptides for substrate recognition. Structural modelling and mutagenesis studies helped identify three residues of catalytic importance in AplG.
NAI-112 是一种糖基化的 III 型聚酮化合物，由一株游动放线菌产生，对伤害性疼痛具有很强的生物活性。它含有两个 labionin/methyllabionin 基序和一个罕见的脱氧己糖修饰，与色氨酸残基 N 连接。在这项研究中，我们通过在大肠杆菌中的异源共表达系统研究了 NAI-112 的生物合成机制的底物耐受性。结果表明，AplKC 是第一个独立催化形成两个 labionin/methyllabionin 基序的 III 型聚酮化合物合成酶。作为一种罕见的 Trp（N）糖基转移酶，AplG 显示出对肽中两个完整环结构的底物识别要求。结构建模和突变研究有助于确定 AplG 中的三个催化重要残基。
