Open AccessDiscovery and Characterization of Bicereucin, an Unusual d -Amino Acid-Containing Mixed Two-Component Lantibiotic
Author(s) -
Liujie Huo,
Wilfred A. van der Donk
Publication year - 2016
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.6b02513
Subject(s) - lantibiotics , lanthionine , chemistry , dehydratase , peptide , biochemistry , amino acid , bacillus cereus , antimicrobial , nisin , enzyme , bacteria , organic chemistry , biology , genetics
Lantibiotics are a group of ribosomally synthesized and post-translationally modified peptides (RiPPs) exhibiting antimicrobial activity. They are characterized by the presence of the thioether-containing bisamino acids lanthionine and methyllanthionine. Here, we report a two-component lantibiotic from Bacillus cereus SJ1 with unusual structural features that we named bicereucin. Unlike all previous two-component lantibiotics, only one of the two peptides of bicereucin contains a lanthionine. The second peptide lacks any cysteines but contains several d-amino acids. These are installed by the dehydrogenase BsjJB, the activity of which was successfully reconstituted in vitro. The proteolytic removal of the leader peptide was also performed in vitro. Bicereucin displayed synergistic antimicrobial activities against Gram-positive strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci as well as hemolytic activity. To illustrate the utility of the enzymes, an analog of the d-amino acid containing opioid dermorphin was successfully produced in E. coli by employing the dehydratase BsjM and the dehydrogenase NpnJA.