<jats:title>ABSTRACT</jats:title> <jats:p> Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the <jats:named-content content-type="genus-species">Bacillus</jats:named-content> group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in <jats:named-content content-type="genus-species">Bacillus cereus</jats:named-content> strain As 1.1846 through genomic mining and PCR screening. The designated <jats:italic>cer</jats:italic> locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor <jats:italic>cerA</jats:italic> genes, one modification gene ( <jats:italic>cerM</jats:italic> ), two processing genes ( <jats:italic>cerT</jats:italic> and <jats:italic>cerP</jats:italic> ), one orphan regulator gene ( <jats:italic>cerR</jats:italic> ), and two immunity genes ( <jats:italic>cerF</jats:italic> and <jats:italic>cerE</jats:italic> ). In addition, one unprecedented quorum sensing component, <jats:italic>comQXPA</jats:italic> , was inserted between <jats:italic>cerM</jats:italic> and <jats:italic>cerR</jats:italic> . The expression of cerecidins was not detected in this strain of <jats:named-content content-type="genus-species">B. cereus</jats:named-content> , which might be due to repressed transcription of <jats:italic>cerM</jats:italic> . We constitutively coexpressed <jats:italic>cerA</jats:italic> genes and <jats:italic>cerM</jats:italic> in <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content> , 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 <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (MDRSA), vancomycin-resistant <jats:named-content content-type="genus-species">Enterococcus faecalis</jats:named-content> (VRE), and even <jats:named-content content-type="genus-species">Streptomyces</jats:named-content> .