Downsizing Class II Lasso Peptides: Genome Mining-Guided Isolation of Huascopeptin Containing the First Gly1-Asp7 Macrocycle

A new
lasso peptide, huascopeptin, was isolated following genome-mined
discovery of a new biosynthetic gene cluster in extremotolerant Streptomyces huasconensis HST28T from Salar de
Huasco, Atacama Desert, Chile. Compound 1 is a 13-residue
class II lasso peptide containing a novel Gly1-Asp7 macrolactam ring,
a three-residue loop, and a three-residue tail, making it the smallest
lasso peptide isolated to date. The lasso structure was confirmed
using NOE restraint-based molecular dynamics simulations.