Furthermore, the LP keeps the modified peptide (mLanA) inactive in the cytosol 9, while the post-translational modifications (PTM) are installed within the CP and not found in the LP 10. The LP serves as a signal sequence and recognition site for the modification enzymes and the export protein 5– 8. Lanthipeptides (LanA) are produced as precursor peptides with an N-terminal leader peptide (LP) and a C-terminal core peptide (CP) 4. The RiPP family of lanthipeptides, especially those with antimicrobial activity (lantibiotics), is gaining interest as a potential alternative for antibiotics to treat harmful multidrug resistance strains such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococci 2, 3. One class of these NPs are ribosomally synthesized and post-translationally modified peptides (RiPPs). as anticancer, antibacterial or antiviral drugs) 1. Many natural products (NP) produced as secondary metabolites by microorganisms can be used as pharmaceuticals (e.g. In summary, this study highlights the pivotal role of NisB for NisT in the secretion process. Additional in vitro studies of the detergent-solubilized NisT revealed how these enzymes and the substrates again influence the activity of transporter. Our determined apparent secretion rates of NisT show how NisB and NisC modulate the transport kinetics of NisA. Here, we present an in vivo secretion analysis of this process in the presence and absence of the nisin maturation machinery, consisting of the dehydratase NisB and the cyclase NisC. Amongst others, the leader peptide is crucial for enzyme recognition and acts as a secretion signal for the ABC transporter NisT that secretes nisin in a proposed channeling mechanism. Nisin is synthesized as a precursor peptide comprising of an N-terminal leader peptide and a C-terminal core peptide. One of the best-studied examples is nisin produced by Lactococcus lactis. Lanthipeptides are ribosomally synthesized and post-translationally modified peptides containing dehydrated amino acids and (methyl-)lanthionine rings.
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