A research status and prospects of edible fungal-derived fibrinolytic enzymes: breakthroughs based on multi-omics and intelligent delivery technologies

Thrombotic diseases represent a significant global health burden. Current clinical thrombolytic agents are plagued by limitations including short half-lives, high bleeding risks, and exorbitant costs. In contrast, fibrinolytic enzymes derived from edible fungi have emerged as a promising research focus, attributed to their superior safety profiles, unique thrombolytic mechanisms, and considerable oral bioavailability potential. Nevertheless, critical bottlenecks such as low enzyme yields in natural strains, suboptimal enzymatic properties, and inefficient in vivo delivery have severely hindered their clinical translation. This review systematically elaborates on strategies to deeply explore and characterize edible fungal fibrinolytic enzyme resources via multi-omics technologies; it also discusses how synthetic biology approaches, including rational engineering of production strains and optimization of heterologous expression systems, can overcome yield limitations. Additionally, the review highlights recent advancements in nanotechnology-based intelligent delivery systems, specifically their roles in enhancing the pharmacokinetic properties of these enzymes, enabling targeted accumulation at thrombotic sites, and facilitating stimuli-responsive release. Finally, it envisions the broad prospects and challenges of interdisciplinary integration in expediting the translation of edible fungal fibrinolytic enzymes from basic research to clinical application.