Representative LC/UV chromatogram under typical analytical conditions (C18 column; mobile phase: 5–100% ACN / H2O (0.05% H3PO4), linear gradient 20 min; flow rate: 0.2 mL/min; detection: 210 nm).
NMR Spectral Data
Representative 1H NMR (500 MHz) spectrum confirming the structure of Lariatin A. Representative 13C NMR (125 MHz) spectrum supporting structural assignment of Lariatin A.
Source Organism
Rhodococcus jostii.
Summary
Lariatin A is a lasso-structured peptide antibiotic active against Mycobacterium species.
Details
Lariatin A is a ribosomally synthesized and post-translationally modified peptide (RiPP) produced by Rhodococcus jostii K01-B0171. It consists of 18 L-amino acids forming a unique lasso structure in which the C-terminal tail (Trp9-Pro18) threads through an N-terminal macrolactam ring formed between Gly1 and the γ-carboxyl group of Glu8. NMR and molecular dynamics studies confirmed this threaded topology. Lariatin A exhibits potent antimycobacterial activity, including inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis (MIC ~0.39 µg/mL). Functional studies demonstrated that Lys17 is essential for antimicrobial activity, likely via salt-bridge interactions stabilizing the lasso conformation. Although the precise intracellular molecular target remains unidentified, lariatin A represents a structurally distinct antimycobacterial peptide scaffold with therapeutic potential.