INVESTIGATION ON PRODUCTION OF RECOMBINANT STREPTOKINASE: PRESENT AND PROSPECT

Abstract

Thrombosis, the blockage of blood vessels with clots, can lead to acute myocardial infarction and ischemic sttoke, both leading causes of death. Other than surgical interventions to remove or by pass the blockage, or the generation  of  collateral  vessels  to  provide  a  new  blood  supply,  the  only  tteatment  available  is  the adininisttation  of  thrombolytic  agents  to  dissolve  the  blood  clot  includuing  stteptokinase,  tPA  (tissue-type plasminogen  activator),  urokinase, taphylokinase,  nattokinase.  Stteptokinase  (SK)  (EC  3.4.99.22)  is  an exttacellular non-enzymatic protein produced by various sttains of p-haemolytic Stteptococci.  SK is a single-

chain protein of molecular weight 47 kDa containing 414 amino acids, having isoelectric pH 4.7. The enzyme has maximum activity between pH 7.3 and 7.6. SK has no proteolytic activity of its own and thus activates PG to PN indirectly by firstly forming a high affinity  equimolar complex with PG (SK-PG activator complex). SK is used broadly as fibrinolytic  agents in hospitals. It is secreted naturally by several P-haemol)ftic  Stteptococci. Low production yield of SK and high risk of natural Stteptococci are the major reasons to produce recombinant SK as an important protein dmg. There were many reports  about cloning, expression  and characterization  of

SK   from   S.   equimilis,  S.  pyrogenes,   S.   uberis  in   E.   coli,  B.   subtilis,  S.   sanguis,  P.   pastoris, Schizosaccharomyces pombe, Lactococcus lactis, Streptomyces lividans. Recently,  in Vietnam  there  are also some research on thrombotic therapy using SK. Quyen Dinh Thi et al,  has cloned, expressed and characterized a  recombinant  SK  in  E.  coli.  Other  thrombotic  agents  including  tPA  and  lumbrokinase  have  been  also investigated by some other research groups in Vietnam.