Lariatin A

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鳳ro18) threads through an N-terminal macrolactam ring formed between Gly1 and the ?-carboxyl group of Glu8. NMR and molecular dynamics studies confirmed this threaded topology. Lariatin A exhibits potent anti-mycobacterial activity, including inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis (MIC ~0.39 ｵg/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 anti-mycobacterial peptide scaffold with therapeutic potential.