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. In this study, 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 re-moval of the leader peptide was also performed in vitro. Bicereucin displayed synergistic anti-microbial activities against gram-positive strains including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) 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.