The widespread and unusual biosynthesis of triculamin-like lasso peptides

Lasso peptides are a growing subclass of ribosomally-synthesized and posttranslationally modified peptides characterized by their lasso-like topology. Our research has found that the biosynthesis of the anti-mycobacterial lasso peptide, triculamin, in Streptomyces is unusual and independent of both leader peptide and leader-dependent proteins. Guided by a bioinformatical survey, we identified diverse biosynthetic gene clusters encoded across Bacillota and Pseudomonadota, resulting in an almost identical lasso peptide despite large differences in the biosynthetic pathway.