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A Robust α-L-Fucosi...
A Robust α-L-Fucosidase from Prevotella nigrescens for Glycoengineering Therapeutic Antibodies
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- Kao, Mu-Rong (författare)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova,Glykovetenskap,School of Pharmacy, College of Pharmacy, Taipei Medical University,Genomics Research Center
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- Ma, Tzu-Hsuan (författare)
- School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wuxing Street, Taipei 11031, Taiwan;Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, Royal Institute of Technology (KTH), AlbaNova University Centre, Stockholm SE-10691, Sweden
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- Chou, Hsiang-Yu (författare)
- School of Pharmacy, College of Pharmacy, Taipei Medical University
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- Chang, Shu-Chieh (författare)
- KTH,Glykovetenskap,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Cheng, Lin-Chen (författare)
- School of Pharmacy, College of Pharmacy, Taipei Medical University
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- Liao, Kuo-Shiang (författare)
- Genomics Research Center, Academia Sinica
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- Shie, Jiun-Jie (författare)
- Institute of Chemistry, Academia Sinica
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- Harris, Philip J. (författare)
- School of Biological Sciences, The University of Auckland
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- Wong, Chi-Huey (författare)
- Genomics Research Center, Academia Sinica, Department of Chemistry, The Scripps Research Institute
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- Hsieh, Yves S. Y. (författare)
- KTH,Glykovetenskap,Wallenberg Wood Science Center,School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wuxing Street, Taipei 11031, Taiwan;Genomics Research Center, Academia Sinica
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: ACS Chemical Biology. - 1554-8929 .- 1554-8937. ; 19:7, s. 1515-1524
- Relaterad länk:
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https://kth.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Eliminating the core fucose from the N-glycans of the Fc antibody segment by pathway engineering or enzymatic methods has been shown to enhance the potency of therapeutic antibodies, especially in the context of antibody-dependent cytotoxicity (ADCC). However, there is a significant challenge due to the limited defucosylation efficiency of commercially available α-l-fucosidases. In this study, we report a unique α-l-fucosidase (PnfucA) from the bacterium Prevotella nigrescens that has a low sequence identity compared with all other known α-l-fucosidases and is highly reactive toward a core disaccharide substrate with fucose α(1,3)-, α (1,4)-and α(1,6)-linked to GlcNAc, and is less reactive toward the Fuc-α(1,2)-Gal on the terminal trisaccharide of the oligosaccharide Globo H (Bb3). The kinetic properties of the enzyme, such as its Km and kcat, were determined and the optimized expression of PnfucA gave a yield exceeding 30 mg/L. The recombinant enzyme retained its full activity even after being incubated for 6 h at 37 °C. Moreover, it retained 92 and 87% of its activity after freezing and freeze-drying treatments, respectively, for over 28 days. In a representative glycoengineering of adalimumab (Humira), PnfucA showed remarkable hydrolytic efficiency in cleaving the α(1,6)-linked core fucose from FucGlcNAc on the antibody with a quantitative yield. This enabled the seamless incorporation of biantennary sialylglycans by Endo-S2 D184 M in a one-pot fashion to yield adalimumab in a homogeneous afucosylated glycoform with an improved binding affinity toward Fcγ receptor IIIa.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Annan kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)
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Kao, Mu-Rong
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Ma, Tzu-Hsuan
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Chou, Hsiang-Yu
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Chang, Shu-Chieh
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Cheng, Lin-Chen
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Liao, Kuo-Shiang
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visa fler...
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Shie, Jiun-Jie
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Harris, Philip J ...
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Wong, Chi-Huey
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Hsieh, Yves S. Y ...
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