Disclosed herein is an expression system for the production and secretion of biologically active clot-specific streptokinase (CSSK) protein in methylotrophic yeast. Yeast-expressed CSSK protein displays improved plasminogen activation and fibrin selectivity. Further disclosed are methylotrophic yeast transformed with at least one copy of functional cDNA sequence encoding CSSK adjunct with modified signal sequence which results in secretion of mature and correctly processed CSSK.