Identification of Targets for Extracellular Proteases Activating Proteins of the Haemostatic System Produced by Micromycetes Aspergillus ochraceus and Aspergillus terreus

Abstract

Effects of extracellular proteases of Aspergillus ochraceus and Aspergillus terreus on plasma hemostasis proteins, consist of initiating the activation of prothrombin complex proteins, was detected. Was discovered, that A. ochraceus proteases have a direct influence on protein C and coagulation factor X, and A. terreus proteases causes their activation indirectly through kallikrein system stimulation. The ability of extracellular proteases of micromycetes activate prekallikrein in human blood plasma on the example of A. terreus was first demonstrated.

Hemostatically Active Proteinase Produced by Aspergillus ochraceus: Key Specific Properties and Effect on Target Proteins

“…In the case of A. ochraceus proteinase, promising in the field of biomedicine, the PAPS can be defined as a proteinase with activating protein C, factor X, and plasmin-like activity. For the proteinase of another Aspergillus , A. terreus , the PAPS of the scope can be designated as a proteinase with activating prekallikrein and plasmin-like activity [ 9 ], and for A. flavus , it can be designated as a proteinase with activating plasminogen and plasmin-like activity [ 11 ].…”

“…Aspergillus proteases are known to exhibit a fibrinolytic effect, as well as to activate protein C, factor X, plasminogen, and prekallikrein. Their physicochemical properties are rather similar; however, the differences in substrate specificity enable considering them as promising agents for diagnostic medicine as exogenous activators of blood plasma proenzymes, as well as to expand the search for potential strains—producers of such enzymes [ 8 , 9 ].…”

Gene Analysis, Cloning, and Heterologous Expression of Protease from a Micromycete Aspergillus ochraceus Capable of Activating Protein C of Blood Plasma

“…Many micromycetes are well known as producers of proteases targeting proteins of the haemostatic system. So, in addition to the fibrinolytic properties of such proteases, the ability of some to activate a number of blood coagulation factors, such as plasminogen [ 47 , 48 ], protein C [ 11 ], prothrombin [ 49 ], prekallikrein [ 50 ], and factor X [ 51 ], is known. Proteolytic enzymes of these micromycetes are capable of cleaving a characteristic range of chromogenic peptide substrates of proteins of the haemostasis system and demonstrate differences in the activity with respect to globular and fibrillar proteins.…”

Secretion of Proteinases with Fibrinolytic Activity by Micromycetes of the Genus Aspergillus

“…Такие различия, полученные при росте микромицета на средах с разными источниками азота, подтверждают высказанное ранее предположение о возможности управлять этим соотношением, изменяя источники азотного питания в составе среды, что может привести к получению более активных по отношению к фибриллярным белкам протеиназ [8]. Сходные значения ФА/ОПА были получены и для другого микромицета -A. ochraceus L-1, известного продуцента протеиназ с фибринолитической и активаторной по отношению к белкам системы гемостаза активностью [15,16]. Полученные данные указывают на значительный биотехнологический потенциал микромицета A. t erreus 2 как продуцента протеиназ с фибринолитической активностью.…”