 ribosomally synthesized and post - translationally modified 
 peptides 
 are a rapidly expanding class of natural products . 
 they are typically 
 biosynthesized by modification of a c - terminal segment of the precursor 
 peptide ( the core peptide ) . 
 the precursor peptide also contains an 
 n - terminal leader peptide that is required to guide the biosynthetic 
 enzymes . for bioengineering purposes , 
 the leader peptide is beneficial 
 because it allows promiscuous activity of the biosynthetic enzymes 
 with respect to modification of the core peptide sequence . 
 however , 
 the leader peptide also presents drawbacks as it needs to be present 
 on the core peptide and then removed in a later step . 
 we show that 
 fusing the leader peptide for the lantibiotic lacticin 481 to its 
 biosynthetic enzyme lctm allows the protein to act on core peptides 
 without a leader peptide . 
 we illustrate the use of this methodology 
 for preparation of improved lacticin 481 analogues containing non - proteinogenic 
 amino acids . 
Supplementary Material