On March 6, the reporter learned from the Tianjin Institute of Industrial Biotechnology of the Chinese Academy of Sciences that the research team of Gao Shushan and the research team of Professor Guo Ruiting of Hangzhou Normal University had made breakthroughs in the research of enzyme catalytic mechanism. For a long time, reactive oxygen species and superoxide anions (O2??) have been regarded as "health killers" in cells. They act like an out of control "molecular scissor", recklessly destroying biomolecules such as DNA and proteins, and are closely related to major diseases such as cancer and aging. However, a recent study by the research team has completely overturned this traditional perception. The team discovered that superoxide anions can actually become "catalysts" for drug synthesis, opening up a new path for green drug manufacturing and synthetic biology. The relevant research results were published in the international academic journal Nature on March 6th Beijing time. Superoxide anions are reactive oxygen species produced during the metabolism of living organisms. Scientists have been continuously researching how to eliminate it in order to reduce its harm to health. However, the research team found that superoxide anions can become efficient biocatalysts under specific conditions, participating in the synthesis of ergotamine drug molecules. It is understood that ergotamine is an important drug molecule, and more than 10 drugs have been developed based on its structure in clinical practice for the treatment of diseases such as massive hemorrhage, Parkinson's disease, and migraine in pregnant women. With the support of structural biology data from the collaborative team Hangzhou Normal University, Gao Shushan first discovered the mystery of the catalase EasC involved in ergotamine synthesis. According to Gao Shushan, EasC has two "workshops": one located in the enzyme center, responsible for producing superoxide anions; The other one is located on the surface of the enzyme and is responsible for catalyzing the synthesis of ergotamine molecules. Two "workshops" are connected by a "transport pipeline", through which superoxide anions are precisely transported to the enzyme surface, initiating the synthesis of drug molecules. The design of this' dual workshop transport pipeline collaborative 'enzyme catalysis method not only utilizes the powerful reaction ability of superoxide anions, but also avoids their destructive nature, reflecting the evolutionary wisdom of microbial enzyme systems in oxygen chemical utilization Gao Shushan said. Further research by the team found that the production process of superoxide anions does not require the consumption of external electrons, but is directly "powered" by ergotamine substrate molecules. Superoxide anions are only produced and transported when the substrate on the enzyme surface is in place. This precise regulatory mechanism not only improves the efficiency of drug synthesis, but also avoids the toxic effects of superoxide anions on cells. This study reveals for the first time the multifunctionality of superoxide anions in biocatalysis, breaking through the traditional understanding of their "negative" functions. Gao Shushan stated that this catalytic mechanism based on superoxide anions may be widely present in different enzyme systems, opening up a new path for the artificial design of efficient biocatalysts. In terms of application, this discovery will accelerate the development of new drugs and green manufacturing processes for antidepressants such as ergotamine. The development of related enzyme preparations will provide a green, low-carbon, and sustainable alternative to traditional chemical synthesis, promoting the paradigm shift of pharmaceutical manufacturing towards high efficiency and environmental protection. Experts in domestic and foreign fields have highly praised this achievement, believing that it "may reshape the understanding of oxidase evolution", and emphasizing that it "opens up a new path for the artificial design of efficient biocatalysts, with significant application potential in fields such as biopharmaceuticals, green chemicals, and new energy development