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Enzyme, therapeutic antibody, homogeneous glycan, protein crystallography, industrial collaboration
NSRRC Scientist Chun-Jung Chen's Collaborative Research on Enzymes Highlighted on JACS Au Cover
2024/07/10
NSRRC Scientist Chun-Jung Chen’s collaborative research on enzymes was highlighted on the cover of JACS Au. The image presents the structural simulation of the newly developed enzyme platform.
Dr. Chun-Jung Chen of the NSRRC conducted a multi-year collaborative project entrusted by OBI Pharma Inc. to explore the structure and function of new enzymes for biomedical applications. This project significantly enhanced the therapeutic activities of antibodies, a breakthrough recently highlighted on the cover of the international journal JACS Au (volume 4, issue 6).

In 2021, four of the top ten best-selling drugs worldwide were monoclonal antibodies (mAbs), including two COVID-19 vaccines. mAb treatments encompass many diseases, including cancers, autoimmune diseases, and infectious diseases. As therapeutic mAbs have gradually dominated the drug market, improvement of their therapeutic efficacy has become a critical issue in the pharmaceutical industry. The research team discovered a novel enzyme from Streptococcus epidemicus. Mutating one key amino acid resulted in excellent transglycosylation activity, allowing the synthesis of homogeneous glycans on mAbs, thus enhancing their medical properties. This advancement can be widely applied to both the existing therapeutic antibodies on the market and those in development.

The NSRRC team led by Dr. Chen, including the co-first author of the research paper Dr. Hong-Hsiang Guan, as well as the major co-authors Dr. Nai-Chi Chen, Dr. Masato Yoshimura, Chien-Chih Lin, and Yen-Chieh Huang, produced enzymes and a series of mutants, and successfully grew crystals with a newly developed pH-jump method. They used TPS 05A, TPS 07A, and TLS 15A1 at the NSRRC and BL44XU at SPring-8 to analyze the structures of enzymes and glycan complexes in various states. For the first time, the step-by-step transglycosylation mechanism of the new enzyme on antibodies was revealed at atomic resolutions.

This novel enzyme could pave the way to establish a highly efficient homogeneous antibody platform, potentially surpassing current medical antibody production processes in the international market and being more self-controllable. As a result, this research significantly contributes to the development of precision medicine. By integrating industrial resources with academic research, the team not only advanced industry-targeted developments but also published high-quality scientific papers, exemplifying a successful NSRRC industrial collaboration.