Characterization of a methyltransferase for iterative N-methylation at the leucinostatin termini in Purpureocillium lilacinum

文献类型： 外文期刊

第一作者： Li, Zixin

作者： Li, Zixin;Jiao, Yang;Ling, Jian;Zhao, Jianlong;Yang, Yuhong;Mao, Zhenchuan;Xie, Bingyan;Li, Yan;Li, Zixin;Zhou, Kaixiang;Wang, Wenzhao

作者机构：

期刊名称：COMMUNICATIONS BIOLOGY （ 影响因子：5.2； 五年影响因子：5.6 ）

ISSN：

年卷期： 2024 年 7 卷 1 期

页码：

收录情况： SCI

摘要： N-methyltransferase (NMT)-catalyzed methylation at the termini of nonribosomal peptides (NRPs) has rarely been reported. Here, we discover a fungal NMT LcsG for the iterative terminal N-methylation of a family of NRPs, leucinostatins. Gene deletion results suggest that LcsG is essential for leucinostatins methylation. Results from in vitro assays and HRESI-MS-MS analysis reveal the methylation sites as NH2, NHCH3 and N(CH3)(2) in the C-terminus of various leucinostatins. LcsG catalysis yields new lipopeptides, some of which demonstrate effective antibiotic properties against the human pathogen Cryptococcus neoformans and the plant pathogen Phytophthora infestans. Multiple sequence alignments and site-directed mutagenesis of LcsG indicate the presence of a highly conserved SAM-binding pocket, along with two possible active site residues (D368 and D395). Molecular dynamics simulations show that the targeted N can dock between these two residues. Thus, this study suggests a method for increasing the variety of natural bioactivity of NPRs and a possible catalytic mechanism underlying the N-methylation of NRPs.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序