Dokdothiocin, an Anti-Neuroinflammatory Thiopeptide from Streptomyces sp. 20A130

Dokdothiocin, a ribosomally synthesized and post-translationally
modified peptide (RiPP) belonging to the thiopeptide family, was isolated
from Streptomyces sp. 20A130. Its structure was elucidated
by extensive NMR analyses, high-resolution mass spectrometry, and
chemical derivatization, revealing a 29-membered macrocyclic scaffold
bearing oxazole, thiazole, and a central pyridine ring. Dokdothiocin
differs from previously reported thiopeptides in macrocycle size,
heterocycle arrangement, and residue-specific modifications, including
the incorporation of a 3-hydroxyproline residue within the macrocyclic
framework. Bioinformatic analysis of the corresponding biosynthetic
gene cluster is consistent with a maturation pathway involving heterocycle
formation and pyridine aromatization. Functionally, dokdothiocin attenuated
lipopolysaccharide-induced activation of BV2 microglial cells by reducing
nitric oxide production and suppressing NF-κB signaling, highlighting
it as a structurally distinctive thiopeptide scaffold with antineuroinflammatory
potential.