Park, Jihun Tran, Son Hung Park, Keunwan Paik, Jin-Hyub Lee, Woong Youn, Jin-Suk Hwang, Gwi Ja Oh, Taehoon Ko, Sung-Kyun Kim, Hiyoung Hong, Young-Soo Kang, Kyungsu Jang, Jun-Pil Jang, Jae-Hyuk 2026-03-27T01:30:06Z 2026-03-27T01:30:06Z 2026-03-24 2026-03 1523-7060 https://pubs.kist.re.kr/handle/201004/154477 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-kappa B signaling, highlighting it as a structurally distinctive thiopeptide scaffold with antineuroinflammatory potential. English American Chemical Society Dokdothiocin, an Anti-Neuroinflammatory Thiopeptide from Streptomyces sp. 20A130 Article 10.1021/acs.orglett.5c05406 1 Organic Letters, v.28, no.10, pp.3117 - 3123 Organic Letters 28 10 3117 3123 N scie scopus Chemistry, Organic Chemistry Article; Early Access NATURAL-PRODUCTS BIOSYNTHESIS