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Functional Genome Mining Reveals a Class V Lanthipeptide Containing a d ‐Amino Acid Introduced by an F 420 H 2 ‐Dependent Reductase
Author(s) -
Xu Min,
Zhang Fei,
Cheng Zhuo,
Bashiri Ghader,
Wang Jing,
Hong Jiali,
Wang Yemin,
Xu Lijun,
Chen Xuefei,
Huang ShengXiong,
Lin Shuangjun,
Deng Zixin,
Tao Meifeng
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202008035
Subject(s) - lantibiotics , lanthionine , dehydroalanine , moiety , biosynthesis , biochemistry , chemistry , reductase , genome , amino acid , cysteine , stereochemistry , gene , enzyme , biology , bacteriocin , bacteria , genetics
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.