Diverse origins of fibrinolytic enzymes: A comprehensive review

Abstract

Fibrinolytic enzymes cleave fibrin which plays a crucial role in thrombus formation which otherwise leads to cardiovascular diseases. While different fibrinolytic enzymes have been purified, only a few have been utilized as clinical and therapeutic agents; hence, the search continues for a fibrinolytic enzyme with high specificity, fewer side effects, and one that can be mass-produced at a lower cost with a higher yield. In this context, this review discusses the physiological mechanism of thrombus formation and fibrinolysis, and current thrombolytic drugs in use. Additionally, an overview of the optimization, production, and purification of fibrinolytic enzymes and the role of Artificial Intelligence (AI) in optimization and the patents granted is provided. This review classifies microbial as well as non-microbial fibrinolytic enzymes isolated from food sources, including fermented foods and non-food sources, highlighting their advantages and disadvantages. Despite holding immense potential for the discovery of novel fibrinolytic enzymes, only a few fermented food sources limited to Asian countries have been studied, necessitating the research on fibrinolytic enzymes from fermented foods of other regions. This review will aid researchers in selecting optimal sources for screening fibrinolytic enzymes and is the first one to provide insights and draw a link between the implication of source selection and in vivo application.

Keywords: Cardiovascular diseases; Fermented foods; Nattokinase; Staphylokinase; Streptokinase; Therapeutic enzymes; Thrombolytic drugs.

Graphical abstract

Fig. 1

A simplified representation of the coagulation system illustrating how clot formation safeguards against blood loss resulting from the vascular injury.

Fig. 2

Geographic distribution of research on fibrinolytic enzymes from fermented foods from the year 2000–2023 (Generated using VOSviewer).