A novel single‐chain enzyme complex with chain reaction properties rapidly producing thromboxane A(2) and exhibiting powerful anti‐bleeding functions

Uncontrollable bleeding is still a worldwide killer. In this study, we aimed to investigate a novel approach to exhibit effective haemostatic properties, which could possibly save lives in various bleeding emergencies. According to the structure‐based enzymatic design, we have engineered a novel single‐chain hybrid enzyme complex (SCHEC), COX‐1‐10aa‐TXAS. We linked the C‐terminus of cyclooxygenase‐1 (COX‐1) to the N‐terminus of the thromboxane A(2) (TXA(2)) synthase (TXAS), through a 10‐amino acid residue linker. This recombinant COX‐1‐10aa‐TXAS can effectively pass COX‐1–derived intermediate prostaglandin (PG) H(2) (PGH(2)) to the active site of TXAS, resulting in an effective chain reaction property to produce the haemostatic prostanoid, TXA(2), rapidly. Advantageously, COX‐1‐10aa‐TXAS constrains the production of other pro‐bleeding prostanoids, such as prostacyclin (PGI(2)) and prostaglandin E(2) (PGE(2)), through reducing the common substrate, PGH(2) being passed to synthases which produce aforementioned prostanoids. Therefore, based on these multiple properties, this novel COX‐1‐10aa‐TXAS indicated a powerful anti‐bleeding ability, which could be used to treat a variety of bleeding situations and could even be useful for bleeding prone situations, including nonsteroidal anti‐inflammatory drugs (NSAIDs)‐resulted TXA(2)‐deficient and PGI(2)‐mediated bleeding disorders. This novel SCHEC has a great potential to be developed into a biological haemostatic agent to treat severe haemorrhage emergencies, which will prevent the complications of blood loss and save lives.