ABSTRACT
Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the
Bacillus
group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in
Bacillus cereus
strain As 1.1846 through genomic mining and PCR screening. The designated
cer
locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor
cerA
genes, one modification gene (
cerM
), two processing genes (
cerT
and
cerP
), one orphan regulator gene (
cerR
), and two immunity genes (
cerF
and
cerE
). In addition, one unprecedented quorum sensing component,
comQXPA
, was inserted between
cerM
and
cerR
. The expression of cerecidins was not detected in this strain of
B. cereus
, which might be due to repressed transcription of
cerM
. We constitutively coexpressed
cerA
genes and
cerM
in
Escherichia coli
, and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistant
Staphylococcus aureus
(MDRSA), vancomycin-resistant
Enterococcus faecalis
(VRE), and even
Streptomyces
.