2019 Fiscal Year Final Research Report
Protein engineering of human FUT8 for efficient production of core fucosylated glycoproteins
| Project/Area Number |
17K06929
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biofunction/Bioprocess
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | フコース転移酵素 / FUT8 / 糖転移酵素 / N型糖鎖 / 翻訳後修飾 |
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| Outline of Final Research Achievements |
We examined to prepare a highly active glycosyltransferase for the functionalization of biopharmaceuticals by modification of N-glycan. As the results, it was found that N-glycosylated human FUT8 mutants have higher activities than the wild type enzyme. In addition, the molecular assembly of FUT8 was investigated, to reveal the mechanism of activation of FUT8 enzyme. It was suggested that human FUT8 potentially forms homodimer via intermolecular hydrophobic interactions involving the α-helical and SH3 domains associated with the catalytic domain.
On the basis of these results, we would like to design more active FUT8 mutants for the development of N-glycan-modified biopharmaceuticals.
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| Free Research Field |
生化学、糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
エリスロポエチンや抗体医薬に代表されるバイオ医薬品の糖鎖改変による機能化が注目されている中、本研究成果は糖鎖改変の主要なツールである糖転移酵素の高活性化に翻訳後修飾改変（本研究ではN型糖鎖改変）が有効であることを示した。また、抗体医薬の機能化に関わるコアフコース構造を合成するFUT8の活性化機構の一つとして、二量体形成が重要であることも明らかにすることができた。これらの成果は、今後のバイオ医薬品の糖鎖改変による機能化技術の発展に有益な情報を提供できるものであると考えられる。
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