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<p><i>Dilong</i> (earthworm) has been widely used in traditional Chinese medicine (TCM) for centuries to treat conditions such as thrombosis, inflammation, and hypertension. Increasing biochemical and pharmacological evidence indicates that these therapeutic effects are largely attributed to a diverse repertoire of bioactive proteins and peptides. These molecules exhibit a broad spectrum of biological activities, including fibrinolytic, anti-inflammatory, antimicrobial, antioxidant, and neuroprotective functions. With advances in omics technologies and protein engineering, growing attention has been directed toward the discovery, functional characterization, and biotechnological production of these macromolecules. This review summarizes recent progress in earthworm-derived proteins and peptides, with an emphasis on their structural diversity, pharmacological properties, and biomedical applications. We further discuss emerging recombinant production strategies and key challenges related to protein folding, secretion, and post-translational modifications. In addition, the integration of artificial intelligence (AI) with synthetic biology for protein design, structure prediction, and pathway optimization is highlighted. These advances collectively provide a foundation for accelerating the translation of earthworm-derived biomolecules into pharmaceutical, cosmetic, and industrial applications.</p> Graphical abstract <p></p>

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Bioactive earthworm proteins and peptides from traditional Chinese medicine: structural diversity, biomedical applications, and emerging biomanufacturing strategies

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Hanzhi Weng,
  • Fengling Yang,
  • Zhiliang Hou,
  • Siyan Zhou,
  • Jie Lu,
  • Xiaoyuan Sun,
  • Ruirui Xu,
  • Zhen Kang

摘要

Dilong (earthworm) has been widely used in traditional Chinese medicine (TCM) for centuries to treat conditions such as thrombosis, inflammation, and hypertension. Increasing biochemical and pharmacological evidence indicates that these therapeutic effects are largely attributed to a diverse repertoire of bioactive proteins and peptides. These molecules exhibit a broad spectrum of biological activities, including fibrinolytic, anti-inflammatory, antimicrobial, antioxidant, and neuroprotective functions. With advances in omics technologies and protein engineering, growing attention has been directed toward the discovery, functional characterization, and biotechnological production of these macromolecules. This review summarizes recent progress in earthworm-derived proteins and peptides, with an emphasis on their structural diversity, pharmacological properties, and biomedical applications. We further discuss emerging recombinant production strategies and key challenges related to protein folding, secretion, and post-translational modifications. In addition, the integration of artificial intelligence (AI) with synthetic biology for protein design, structure prediction, and pathway optimization is highlighted. These advances collectively provide a foundation for accelerating the translation of earthworm-derived biomolecules into pharmaceutical, cosmetic, and industrial applications.

Graphical abstract