Functional Genome Mining Reveals a Class V Lanthipeptide Containing a <scp>d</scp>‐Amino Acid Introduced by an F<sub>420</sub>H<sub>2</sub>‐Dependent Reductase
Min Xu, Fei Zhang, Zhuo Cheng, Ghader Bashiri, Jing Wang, Jiali Hong, Yemin Wang, Lijun Xu, Xuefei Chen, Sheng‐Xiong Huang, Shuangjun Lin, Zixin Deng, Meifeng Tao
Abstract
Abstract Lantibiotics are a type of ribosomally synthesized and post‐translationally modified peptides (termed lanthipeptides) with often potent antimicrobial activity. Herein, we report the discovery of a new lantibiotic, lexapeptide, using the library expression analysis system (LEXAS) approach. Lexapeptide has rare structural modifications, including N‐terminal ( N , N )‐dimethyl phenylalanine, C‐terminal (2‐aminovinyl)‐3‐methyl‐cysteine, and d ‐Ala. The characteristic lanthionine moiety in lexapeptide is formed by three proteins (LxmK, LxmX, and LxmY), which are distinct from enzymes known to be involved in lanthipeptide biosynthesis. Furthermore, a novel F 420 H 2 ‐dependent reductase (LxmJ) from the lexapeptide biosynthetic gene cluster (BGC) is identified to catalyze the reduction of dehydroalanine to install d ‐Ala. Our findings suggest that lexapeptide is the founding member of a new class of lanthipeptides that we designate as class V. We also identified further class V lanthipeptide BGCs in actinomycetes and cyanobacteria genomes, implying that other class V lantibiotics await discovery.