Abstract
Lantibiotics are ribosomally synthesized antimicrobial peptides secreted by mainly Gram-positive bacteria. Class 1 lantibiotics mature via two modification steps introduced by a modification LanBC complex. For the lantibiotic nisin, the dehydratase NisB catalyzes the dehydration of serine and threonine residues in the so-called core peptide. Second, five (methyl)-lanthionine rings are introduced in a regio- and stereospecific manner by the cyclase NisC. Here, we characterized the assembly of the NisBC complex in vitro, which is only formed in the presence of the substrate. The complex is composed of a NisB dimer, a monomer of NisC and one prenisin molecule. Interestingly, the presence of the last lanthionine ring prevented complex formation. This stoichiometry was verified by small-angle X-ray scattering measurements, which revealed the first structural glimpse of a LanBC complex in solution.
Highlights
Lantibiotics are ribosomally synthesized antimicrobial peptides secreted by mainly Gram-positive bacteria
Bacteriocins are a group of antimicrobial peptides produced by Gram-positive as well as Gram-negative bacteria and some of them undergo posttranslational modifications (PTM(s))[1,2]
Common to all class I lantibiotics is a N-terminal leader sequence, which is crucial for the recognition by the PTM enzymes, secretion and for keeping the peptide in an inactive state within the cell
Summary
Lantibiotics are ribosomally synthesized antimicrobial peptides secreted by mainly Gram-positive bacteria. Lanthipeptides contain the non-natural amino acids lanthionine or (methyl)-lanthionine and in case that they display antimicrobial activity, these peptides are called lantibiotics[3,4] They are classified in four different classes (Type I-IV) depending on the enzymes involved in the PTM(s)[3,4]. The enzyme LanB dehydrates serine or threonine residues, whereas LanC catalyzes the thioether ring formation of the dehydrated amino acid and a C-terminally located cysteine residue within the core peptide via a Michael addition reaction[5] This results in the formation of lanthionine (from Ser) or (methyl)-lanthionine (from Thr) rings, which are crucial for the activity as well as stability[6,7,8,9,10,11,12]. The entire maturation process is schematically summarized in www.nature.com/scientificreports/
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