Triculamin: An Unusual Lasso Peptide with Potent Antimycobacterial Activity
Frederikke D. Andersen, Katja D. Pedersen, Dennis Wilkens Juhl, Tobias Mygind, Paul Chopin, Esben B. Svenningsen, Thomas B. Poulsen, M. Lund, Andreas Schramm, Charlotte H. Gotfredsen, Thomas Tørring
Abstract
Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) produced by microorganisms. Here we show that the two natural products triculamin and alboverticillin, originally isolated in 1967 and 1958, respectively, with potent and specific activity against mycobacteria are in fact the same lasso peptide. We solved the structure using 2D NMR spectroscopy and expanded on the previously reported bioactivity. Through genome sequencing, we identify the responsible biosynthetic gene clusters, which curiously revealed that, unlike any known lasso peptides, their precursor peptides appear to have a follower instead of a leader peptide.