Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 11 min ago
Peer-reviewedCC BY-NC-NDNature communications

Genome-directed discovery of an octalin-containing polyether ionophore improves diabetic skin wound healing.

  • Chunyan Fang1,2,3
  • Zhiwen Liu1,2,3,4
  • Liangliang Bai5,6,7
  • Liang Ma1,2,3,4
  • Weiliang Xiong1,2
  • Lili Sun1,2,4
  • Linping Wu8
  • Jing Ni8
  • Wenjun Zhang1,2,3,4
  • Yiguang Zhu1,2,3,4,9
  • Yanxin Luo10,11
  • Yingjie Li12
1 more authors
  • Changsheng Zhang13,14,15,16,17
17 affiliations
  1. 1State Key Laboratory of Tropical Oceanography, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
  2. 2Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
  3. 3Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya, China.
  4. 4University of Chinese Academy of Sciences, Beijing, China.
  5. 5Department of Pharmacy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  6. 6Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  7. 7Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  8. 8China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  9. 9China Sri Lanka Joint Center for Education and Research, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
  10. 10Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. [email protected].
  11. 11Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. [email protected].
  12. 12China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. [email protected].
  13. 13State Key Laboratory of Tropical Oceanography, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. [email protected].
  14. 14Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. [email protected].
  15. 15Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya, China. [email protected].
  16. 16University of Chinese Academy of Sciences, Beijing, China. [email protected].
  17. 17China Sri Lanka Joint Center for Education and Research, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China. [email protected].
Read full textPDFDOICite

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.

Related

  1. Directed effective connectivity between the SCN-containing hypothalamus and pineal gland varies by chronotype in bipolar disorder
    I. Mehrdadi, S. Kuster, J. Rohrer +5
    medRxivPreprintCC BYFull textPsychiatry & mental healthmedRxiv
  2. Novel Allulose- and Amino Acid-Containing Sugar-Free Electrolyte Beverage Improves Body Water Restoration in Ad Libitum Rehydration Following Exercise-Induced Dehydration
    Sajjad Rezaei, Sai Tejaswari Gopalakrishnan, Parker Kooima +9
    NutrientsPeer-reviewedCC BY 4.0NutritionCrossref
  3. Discovery of a Peripherally Directed CB1 Receptor Antagonist That Restores Insulin Signaling in Adipocytes
    Jhonny Azuaje, Rubén Prieto-Díaz, Claudia Gioé-Gallo +17
    ACS OmegaPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossrefDOAJPMC
  4. Cytotoxic Interactions Between Cannabidiol and Ionophore Coccidiostats in Feline and Canine Kidney Cell Lines—An In Vitro Study
    Lidia Radko, Oliwia Kończak, Ovinuchi Ejiohuo +2
    MoleculesPeer-reviewedCC BY 4.0Pharmacology & toxicologyCrossref
  5. Intake of foods containing phytochemicals is correlated with benign prostatic hyperplasia development: a long-term follow-up study
    Tomiyo Nakamura, Akiko Shiotani, Chikako Yasui +2
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textGeneral medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{fang2026genomedirected,
  title = {{Genome-directed discovery of an octalin-containing polyether ionophore improves diabetic skin wound healing.}},
  author = {Chunyan Fang and Zhiwen Liu and Liangliang Bai and Liang Ma and Weiliang Xiong and Lili Sun and Linping Wu and Jing Ni and Wenjun Zhang and Yiguang Zhu and Yanxin Luo and Yingjie Li and Changsheng Zhang},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77444-w},
  url = {https://europepmc.org/article/MED/42897161},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Genome-directed discovery of an octalin-containing polyether ionophore improves diabetic skin wound healing.
AU  - Chunyan Fang
AU  - Zhiwen Liu
AU  - Liangliang Bai
AU  - Liang Ma
AU  - Weiliang Xiong
AU  - Lili Sun
AU  - Linping Wu
AU  - Jing Ni
AU  - Wenjun Zhang
AU  - Yiguang Zhu
AU  - Yanxin Luo
AU  - Yingjie Li
AU  - Changsheng Zhang
PY  - 2026
DA  - 2026/09/09
JO  - Nature communications
DO  - 10.1038/s41467-026-77444-w
UR  - https://europepmc.org/article/MED/42897161
AB  - 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.
SN  - 2041-1723
ER  -