Zn-dependent bifunctional proteases are responsible for leader peptide processing of class III lanthipeptides

作者：Shaoming Chen, Bing Xu, Erquan Chen, Jiaqi Wang, Jingxia Lu, Stefano Donadio, Hui Ming Ge, Huan Wang · 发表于：Proceedings of the National Academy of Sciences · 年份：2019 · DOI：10.1073/pnas.1815594116 · 被引用次数：64 · 研究领域：Microbial Natural Products and Biosynthesis、Biochemical and Structural Characterization、Chemical Synthesis and Analysis

Significance Lanthipeptides represent one of the largest classes of peptide natural products with a ribosomal origin, and their maturation requires a designated protease(s) to remove the N-terminal leader peptides after core peptide modifications are properly installed. For class III lanthipeptides, the identity of the protease(s) responsible for leader processing remains unclear, posing a major obstacle to their heterologous production and bioengineering. This study reveals that an unprecedented class of bifunctional Zn-dependent proteases is universally responsible for the leader removal of class III lanthipeptides, thereby clarifying the long-standing question regarding the biosynthesis of this emerging group of natural products. Our study should facilitate the discovery and bioengineering of class III lanthipeptides in the future.