Supported by key projects of the National Natural Science Foundation of China, the Institute of Biology and Chemical Engineering at Tsinghua University has successfully developed China's first intelligent multifunctional enzyme—MBP (maltose-binding protein) fusion heparinase. Following six months of pilot testing, the research team has consistently produced ultra-low molecular weight heparin with an average molecular weight ranging from 2000 to 3000, reaching international advanced standards.
Enzymatic catalysis plays a crucial role in advancing green chemistry. For many years, low molecular weight heparin, a critical drug for preventing and treating thrombosis in China, has been heavily reliant on imports, resulting in high costs. This development holds significant social value. According to reports, the research team utilized biochemical technology to create a new, efficient, and intelligent process for producing MBP fusion heparinase. They introduced a fluorescent protein signal to the enzyme, enabling quick tracking. Additionally, they incorporated the easily separable MBP protein, allowing the heparinase to be purified in just one step, achieving high purity.
After half a year of industrial testing, the MBP fusion heparinase developed by the institute not only effectively degrades heparin but also enables the preparation of ultra-low molecular weight heparin with an average molecular weight of 2000–3000 by adjusting reaction time and enzyme dosage. Notably, the enzymatic method is mild compared to traditional chemical lysis techniques, offering advantages such as high yield, environmental friendliness, and the potential for continuous production. Moreover, the product and the enzyme can be easily separated, allowing the enzyme to be reused, which significantly reduces both enzyme and production costs.
This intelligent, multifunctional MBP fusion heparinase has already secured three patents and was awarded the Silver Prize at the 17th National Invention Exhibition in November 2007.
Currently, the research group is applying this intelligent enzyme to the transformation of phosphotransferases and industrial enzymes. In the context of phosphotransferases used in the food additive industry, domestic chemical methods often produce toxic substances, while biological methods are dominated by Japan and South Korea. With the help of intelligent, multifunctional phosphotransferases, the activity of the enzyme can be monitored in real-time, and the reaction conditions are mild, clean, and pollution-free.
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