Discovery and Characterization of Bicereucin, an Unusual d-Amino Acid-Containing
Mixed Two-Component Lantibiotic
#MMPMID27074593
Huo L
; van der Donk WA
J Am Chem Soc
2016[Apr]; 138
(16
): 5254-7
PMID27074593
show ga
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.
free
free
free
