Sharma Chhavi, Osmolovskiy Alexander, Singh Rajni
Amity Institute of Microbial Technology, Amity University Uttar Pradesh, Noida 201313, India.
Department of Microbiology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Pharmaceutics. 2021 Nov 5;13(11):1880. doi: 10.3390/pharmaceutics13111880.
Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes.
诸如急性心肌梗死、栓塞和中风等心脏疾病主要归因于血管中纤维蛋白过度积累，通常会导致血栓形成。包括使用抗凝血剂、抗血小板药物、外科手术和纤维蛋白溶解酶在内的多种方法被用于溶解纤维蛋白凝块，从而改善血栓形成。由于典型抗血栓策略存在不良后遗症且成本高昂，微生物纤维蛋白溶解酶在心血管疾病治疗中比典型抗血栓策略更受关注。纤维蛋白溶解酶如纤溶酶原激活剂和类纤溶酶蛋白能高效水解血栓，且无明显后遗症，并且可以在短时间内以低成本大规模生产。然而，寻找新型纤维蛋白溶解酶需要复杂的纯化步骤、理化和结构功能特性，这有助于深入了解它们的作用机制。此外，通过菌株改良以及克隆、过表达和构建转基因菌株等分子技术来提高纤维蛋白溶解酶的产量，可显著提升其溶栓潜力。此外，一些纤维蛋白溶解酶的非常规适用性为其除了用于纤维蛋白/血栓水解之外，还开辟了用于蛋白质水解、血压调节、抗菌、去除血渍的洗涤剂添加剂、预防龋齿、抗炎和黏液溶解祛痰剂等领域的道路。因此，这篇综述文章涵盖了微生物纤维蛋白溶解酶的生产、生化/结构功能特性、溶栓潜力及其他额外应用。
