LASSO

Lasso peptides are a class of peptides produced by bacteria that share a very original structure with a high stability, which display different biological activities as antimicrobial peptides, receptor antagonists or enzyme inhibitors. We have recently achieved the first in vitro reconstitution of a lasso peptide and proposed a common biosynthesis pathway for this class of peptides. This pathway involves the ribosomal production of a precursor, followed by a maturation step involving two enzymes. The biosynthesis of lasso peptides represents an attractive biotechnology given the high stability and panel of biological activities of such peptides. Our project aims at using microcin J25, an antibacterial peptide that inhibits the RNA polymerase, (i) as model to characterise the molecular mechanisms involved in lasso peptide biosynthesis and (ii) as template to formalize the structural features involved in lasso peptides activity, through structure/activity relationships involving state-of-the-art NMR and mass spectrometry methods. Our results should permit to use the lasso structure as a template for the design of bioactive peptides.