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Enzyme Engineering Strategies for the Bioenhancement of l-Asparaginase Used as a Biopharmaceutical

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Abstract

Over the past few years, there has been a surge in the industrial production of recombinant enzymes from microorganisms due to their catalytic characteristics being highly efficient, selective, and biocompatible. l-asparaginase (l-ASNase) is an enzyme belonging to the class of amidohydrolases that catalyzes the hydrolysis of l-asparagine into l-aspartic acid and ammonia. It has been widely investigated as a biologic agent for its antineoplastic properties in treating acute lymphoblastic leukemia. The demand for l-ASNase is mainly met by the production of recombinant type II l-ASNase from Escherichia coli and Erwinia chrysanthemi. However, the presence of immunogenic proteins in l-ASNase sourced from prokaryotes has been known to result in adverse reactions in patients undergoing treatment. As a result, efforts are being made to explore strategies that can help mitigate the immunogenicity of the drug. This review gives an overview of recent biotechnological breakthroughs in enzyme engineering techniques and technologies used to improve anti-leukemic l-ASNase, taking into account the pharmacological importance of l-ASNase.

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Acknowledgements

Thanks to ANID (Agencia Nacional de Investigación y Desarrollo) Master Scholarship, (grant number 22220584).

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Authors and Affiliations

  1. Chemical Engineering Department, Universidad de la Frontera, Francisco Salazar 1145, 4811230, Temuco, Región de la Araucanía, Chile

    Javiera Miranda, Nicolás Lefin, Jorge F. Beltran, Jorge G. Farias & Mauricio Zamorano

  2. Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile

    Lisandra Herrera Belén

  3. Department of Civil and Environmental Engineering, University of Cyprus, Nicosia, Cyprus

    Argyro Tsipa

Authors
  1. Javiera Miranda
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  2. Nicolás Lefin
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  3. Jorge F. Beltran
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  4. Lisandra Herrera Belén
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  5. Argyro Tsipa
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  6. Jorge G. Farias
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  7. Mauricio Zamorano
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Corresponding author

Correspondence to Mauricio Zamorano.

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Funding

The authors thank the Chemical Engineering Department, Universidad de La Frontera, Temuco, Chile, for financial support. This study was funded by FAPESP-UFRO project no. 2020/06982-3

Conflict of interest/Competing interests

Javiera Miranda, Nicolás Lefin, Jorge F. Beltran, Lisandra Herrera Belén, Argyro Tsipa, Jorge G. Farias, and Mauricio Zamorano declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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JM, NL, JFB, LBH, AT, JGF, and MZ hereby provide consent for the publication of this manuscript.

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Drafting of the manuscript: JM. Conception and design: JM, MZ. Editing of the manuscript: MZ. All authors reviewed and approved the manuscript.

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Miranda, J., Lefin, N., Beltran, J.F. et al. Enzyme Engineering Strategies for the Bioenhancement of l-Asparaginase Used as a Biopharmaceutical. BioDrugs 37, 793–811 (2023). https://doi.org/10.1007/s40259-023-00622-5

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