{ "abstract": "Chronic hard-to-heal skin wounds in diabetes mellitus pose a significant clinical challenge, underscoring the urgent need for additional therapeutics. Herein, we report the identification of a polyether biosynthetic gene cluster (pdm BGC) from the marine-derived Streptomyces marincola SCSIO 03032 through genome mining. By overexpressing the positive regulator gene pdmRI, we increase the product of the pdm BGC 48-fold to enable the isolation, structural determination, and biosynthesis investigation of an octalin-containing polyether ionophore polydecalinmycin (PDM). Functionally, PDM demonstrates remarkable efficacy in promoting acute skin wound healing in BALB/c mice and significantly accelerating chronic wound closure in a diabetic mouse (db/db, male) model. Mechanistically, PDM induces an elevation of mitochondrial Na⁺ levels to trigger a transient burst of reactive oxygen species, a critical signal for initiating acute wound closure. Upon prolonged exposure, PDM activates a robust Nrf2-mediated antioxidant response, restoring mitochondrial homeostasis and conferring cytoprotection against high-glucose-induced oxidative stress. These insights highlight the therapeutic potential of PDM as a natural polyether candidate for developing ionophore-based strategies for diabetic wound healing.", "abstract_shown": true, "affiliations": [ "State Key Laboratory of Tropical Oceanography, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.", "Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.", "Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya, China.", "University of Chinese Academy of Sciences, Beijing, China.", "Department of Pharmacy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.", "China Sri Lanka Joint Center for Education and Research, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.", "Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. luoyx25@mail.sysu.edu.cn.", "Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. luoyx25@mail.sysu.edu.cn.", "China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. li_yingjie@gibh.ac.cn.", "State Key Laboratory of Tropical Oceanography, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. czhang2006@gmail.com.", "Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. czhang2006@gmail.com.", "Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya, China. czhang2006@gmail.com.", "University of Chinese Academy of Sciences, Beijing, China. czhang2006@gmail.com.", "China Sri Lanka Joint Center for Education and Research, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. czhang2006@gmail.com." ], "article_type": "research support, non u.s. gov't", "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0, 1, 2 ], "name": "Chunyan Fang", "orcid": "0000-0002-3386-2331" }, { "affs": [ 0, 1, 2, 3 ], "name": "Zhiwen Liu" }, { "affs": [ 4, 5, 6 ], "name": "Liangliang Bai" }, { "affs": [ 0, 1, 2, 3 ], "name": "Liang Ma" }, { "affs": [ 0, 1 ], "name": "Weiliang Xiong" }, { "affs": [ 0, 1, 3 ], "name": "Lili Sun" }, { "affs": [ 7 ], "name": "Linping Wu", "orcid": "0000-0001-7579-2987" }, { "affs": [ 7 ], "name": "Jing Ni" }, { "affs": [ 0, 1, 2, 3 ], "name": "Wenjun Zhang" }, { "affs": [ 0, 1, 2, 3, 8 ], "name": "Yiguang Zhu" }, { "affs": [ 9, 10 ], "name": "Yanxin Luo", "orcid": "0000-0002-5200-3997" }, { "affs": [ 11 ], "name": "Yingjie Li", "orcid": "0000-0003-3386-0210" }, { "affs": [ 12, 13, 14, 15, 16 ], "name": "Changsheng Zhang", "orcid": "0000-0003-2349-3138" } ], "bibtex": "https://research.draconitic.com/paper/7n98j5dxd4qdh.bib", "cited_by": 0, "doi": "10.1038/s41467-026-77444-w", "fulltext_url": "https://europepmc.org/articles/PMC13680505", "id": "7n98j5dxd4qdh", "issns": [ "2041-1723" ], "landing_url": "https://europepmc.org/article/MED/42897161", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2736|Microbial Natural Products and Biosynthesis" ] ], "openalex": "W7212015177", "pdf_url": "https://europepmc.org/articles/PMC13680505?pdf=render", "pmcid": "PMC13680505", "pmid": "42897161", "published": "2026-09-09", "publisher": null, "ris": "https://research.draconitic.com/paper/7n98j5dxd4qdh.ris", "sources": [ { "first_seen": "2026-10-30T12:19:41Z", "native_id": "MED:42897161", "source": "europepmc", "url": "https://europepmc.org/article/MED/42897161" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2736|Microbial Natural Products and Biosynthesis", "subfield": "pharmacology-toxicology" } ], "title": "Genome-directed discovery of an octalin-containing polyether ionophore improves diabetic skin wound healing.", "title_text": "Genome-directed discovery of an octalin-containing polyether ionophore improves diabetic skin wound healing.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:41Z", "url": "https://research.draconitic.com/paper/7n98j5dxd4qdh", "venue": "Nature communications", "versions": [] }