Original Research Article Food Origin Fibrinolytic Enzyme With Multiple Actions Laurentia Stephani, 1 ,2 Raymond Rubianto Tjandrawinata, 3 Diana Nur Afifah, 1 Yanti Lim, 2 Wangsa Tirta Ismaya, 3 Maggy Thenawidjaja Suhartono 1* 1 Department of Food Science and Technology, Bogor Agricultural University, Darmaga Campus Bogor, Indonesia. 2 Faculty of Biotechnology, Atmajaya University, Jakarta, Indonesia. 3 Dexa Laboratories of Biomolecular Sciences, Dexa Medica Jababeka Cikarang, Jakarta, Indonesia. article info Article history: Received 19 May 2017 Received in revised form 29 August 2017 Accepted 3 September 2017 Available online 29 September 2017 KEYWORDS: enzyme, fibrinolytic, Oncom, Stenotrophomonas abstract Many health related problems such as cardiovascular diseases are associated with the formation of excessive clot in the blood (thrombus). Approaches in cardiovascular disease treatment are preventing the formation or removing the thrombus. The present thrombolytic agents can be classified as plasminogen activators, fibrinolytic enzyme which directly degrades fibrinogen or fibrin and heparin type which act as thrombin inhibitor. Recently, microbial fibrinolytic enzymes of food origin receive more attention that leads to escalating efforts to explore traditional fermented foods as the natural sources. We have suc- cessfully isolated microorganism from Indonesian fermented soybean tofu dregs “Oncom” that secretes fibrinolytic enzyme. The microorganism identified as Stenotrophomonas sp. is unique because most of the reported fibrinolytic microorganism belongs to Bacillus sp. This isolate was found to produce extracellular fibrinolytic enzyme which could degrade fibrinogen and fibrin directly as determined by fibrinogen zymography and fibrin plate methods. More importantly, the 30-kD purified enzymes was found to demonstrate not only fibrin and fibrinogen degradation capabilities, but also acted as thrombin inhibitor as determined using specific substrates for thrombin. This is the first report of a fibrinolytic enzyme that demonstrates additional synergistic activities. This finding accentuates the importance of further devel- opment of the enzyme into a powerful agent to treat the thrombus-related disease effectively. Copyright © 2017 Institut Pertanian Bogor. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction A variety of diseases and health problems are influenced by reactions that maintain a balance between blood coagulation and anticoagulation. Coagulation process produces fibrin-containing blood clots which is formed from fibrinogen by thrombin catalysis (Lioudaki and Ganotakis 2010; Voet and Voet 1990; Wang et al. 2006). Fibrin can be dissolved by fibrinolytic enzymes such as plasmin, which is normally activated from the nonactive plasmin- ogen by a tissue-type plasminogen activator (tPA) (Collen and Lijnen 2004; Nakajima et al. 1993; Wang et al. 2011). This process maintains blood flow at vascular injury sites and is an important component of the normal haemostatic responses. Disturbances in the anticoagulation process can lead to accumulation of fibrin in the blood vessels and results as thrombosis conditions which usually lead to myocardial infarction and other cardiovascular diseases (Collen and Lijnen 2004; Kim et al. 1996). Researches are continu- ously pursued to find fibrinolytic agents, plasminogen activators and thrombin inhibitors which are safe and can work efficiently. Tissue plasminogen activator (tPA) is a serine protease which catalyses the conversion of plasminogen to plasmin, a major enzyme responsible for breakdown of fibrin in the blood clots. Plasminogen activators, such as tPA, urokinase, alteplase and reteplase are used in the clinical medicine to treat embolic and thrombotic strokes (Dubey et al. 2011; Duffy 2002; deMers 2012). Thrombin has many important functions in the clotting pathway leading to formation of the insoluble fibrin clots, so it is a good target for anticoagulants drugs. Natural antithrombin (AT) is a small protein molecule of 58 kDa that inactivates several enzymes of the coagulation system. ATs are required not only for blood disease disorder, arterial and deep vein thrombosis or coronary syndromes, but also during sepsis conditions which is known to activate the * Corresponding author. E-mail address: mthenawidjaja@yahoo.com (M.T. Suhartono). Peer review under responsibility of Institut Pertanian Bogor. HOSTED BY Contents lists available at ScienceDirect HAYATI Journal of Biosciences journal homepage: http://www.journals.elsevier.com/ hayati-journal-of-biosciences https://doi.org/10.1016/j.hjb.2017.09.003 1978-3019/Copyright © 2017 Institut Pertanian Bogor. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). HAYATI Journal of Biosciences 24 (2017) 124e130