Lantibiotics represent a class of peptide antibiotics that shows promising antimicrobial activity against Gram-positive pathogens, e.g., Staphylococcus aureus or Clostridium difficile (Castiglione et al., 2007; Bierbaum and Sahl, 2009). The best studied example is nisin, synthesized by the Gram-positive bacterium Lactococcus lactis. It belongs to the class of RiPPs and is translated as a precursor comprising a 23 amino acid leader peptide fused to a 34 amino acid core peptide. The leader serves as a docking station for the modification enzymes, directs the transport of the peptide out of the cell, and keeps it inactive to prevent activity against the producer strain (Bierbaum and Sahl, 2009; Ortega et al., 2015). Within the core peptide, specific serine and threonine residues are dehydrated by the dehydratase NisB to form dehydroalanine (Dha) and dehydrobutyrine (Dhb). In a cyclization reaction catalyzed by the cyclase NisC, these unusual amino acid derivatives are combined with the next downstream cysteine to form the five characteristic (methyl)lanthionine rings which are essential for bioactivity. The post-translationally modified peptide is transported out of the cell by the transporter NisT. Finally, the leader peptide is cleaved off by the membrane-associated protease NisP, to release active nisin (see Figure 1A for a schematic structure of fully modified active nisin) (Lubelski et al., 2008).