Nature Communications (Apr 2025)
A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus
- Mingqing Tang,
- Guoxing Ma,
- Chunyan Xu,
- Hui Yang,
- Hongjun Lin,
- Chao Bian,
- Chengjia Hu,
- Meiling Lu,
- Lei Chen,
- Wencai Jie,
- Zhen Yue,
- Jianbo Jian,
- Yuqing Sun,
- Hui Yan,
- Jingjing Zhou,
- Xianying Zhang,
- Shengye Liao,
- Zhaofa Li,
- Shuangfeng Cai,
- Yaqing Wu,
- Kexin Yang,
- Yanan Xiong,
- Yonggang Zhao,
- Zhimin Lv,
- Xiaoming Xu,
- Chuang Liu,
- Pengliang Xin,
- Lichao Ye,
- Xiuling Cui,
- Qiong Shi,
- Xi Chen,
- Ruian Xu
Affiliations
- Mingqing Tang
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Guoxing Ma
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Chunyan Xu
- BGI Research
- Hui Yang
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University
- Hongjun Lin
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Chao Bian
- Laboratory of Aquatic Genomics, College of Life Sciences and Oceanography, Shenzhen University
- Chengjia Hu
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Meiling Lu
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Lei Chen
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Wencai Jie
- BGI Genomics
- Zhen Yue
- BGI Research
- Jianbo Jian
- BGI Genomics
- Yuqing Sun
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Hui Yan
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Jingjing Zhou
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Xianying Zhang
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Shengye Liao
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Zhaofa Li
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Shuangfeng Cai
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Yaqing Wu
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Kexin Yang
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Yanan Xiong
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Yonggang Zhao
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Zhimin Lv
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Xiaoming Xu
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Chuang Liu
- The First Affiliated Hospital of Zhengzhou University
- Pengliang Xin
- Department of Haematology, Quanzhou First Hospital Affiliated to Fujian Medical University
- Lichao Ye
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University
- Xiuling Cui
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- Qiong Shi
- Laboratory of Aquatic Genomics, College of Life Sciences and Oceanography, Shenzhen University
- Xi Chen
- Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University
- Ruian Xu
- Engineering Research Centre of Molecular Medicine of Ministry of Education, Fujian Key Laboratory of Molecular Medicine, Key Laboratory of Precision Medicine and Molecular Diagnosis of Fujian Universities, Xiamen Key Laboratory of Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University
- DOI
- https://doi.org/10.1038/s41467-025-58915-y
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 19
Abstract
Abstract Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin–activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus. Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.