Enhancement of reciprocal activation of prourokinase and plasminogen by the bacterial lipopeptide surfactins and iturin Cs.

Urokinase-type plasminogen activator (u-PA) is a serine protease that cleaves Arg561-Val562 bond in plasminogen to convert it to the active serine protease plasmin, which is involved not only in blood clot dissolution but also in a variety of physiological and pathological processes requiring localized proteolysis1). u-PA is synthesized and secreted as a single-chain zymogen form (pro-u-PA)2). Prou-PA is proteolytically activated (by cleavage at Lys158Ile159) into a two-chain form (tcu-PA) by plasmin2,3). It is postulated that pro-u-PA has a slight intrinsic proteolytic activity to convert plasminogen to plasmin4,5). The reciprocal activation of pro-u-PA and plasminogen provides a mechanism for initiation and localized propagation of fibrinolysis and matrix proteolysis. We screened microorganisms for their ability to produce low molecular weight compound that enhances the reciprocal activation of pro-u-PA and plasminogen and identified surfactin C as an active compound. Surfactin C enhances the reciprocal reaction by modulating plasminogen conformation. This effect leads to elevation of fibrinolysis both in vitro and in vivo6). In this study, we have identified and characterized several other bacterial lipopeptides (isohalobacillin and iturins C2 and C4, as well as four surfactins).