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L-asparaginase production review: bioprocess design and biochemical characteristics

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Abstract

In the past decades, the production of biopharmaceuticals has gained high interest due to its great sensitivity, specificity, and lower risk of negative effects to patients. Biopharmaceuticals are mostly therapeutic recombinant proteins produced through biotechnological processes. In this context, L-asparaginase (L-asparagine amidohydrolase, L-ASNase (E.C. 3.5.1.1)) is a therapeutic enzyme that has been abundantly studied by researchers due to its antineoplastic properties. As a biopharmaceutical, L-ASNase has been used in the treatment of acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), and other lymphoid malignancies, in combination with other drugs. Besides its application as a biopharmaceutical, this enzyme is widely used in food processing industries as an acrylamide mitigation agent and as a biosensor for the detection of L-asparagine in physiological fluids at nano-levels. The great demand for L-ASNase is supplied by recombinant enzymes from Escherichia coli and Erwinia chrysanthemi. However, production processes are associated to low yields and proteins associated to immunogenicity problems, which leads to the search for a better enzyme source. Considering the L-ASNase pharmacological and food importance, this review provides an overview of the current biotechnological developments in L-ASNase production and biochemical characterization aiming to improve the knowledge about its production.

Key points

• Microbial enzyme applications as biopharmaceutical and in food industry

• Biosynthesis process: from the microorganism to bioreactor technology

• Enzyme activity and kinetic properties: crucial for the final application

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Acknowledgements

Valéria C. Santos-Ebinuma, Danielle B. Pedrolli, Gabriela B. de Paiva, and Heitor B. S. Bento acknowledge FAPESP, CNPq (National Council for Scientific and Technological Development, Brazil), and CAPES (Coordination of Superior Level Staff Improvement, Brazil).

Funding

This work was funded by the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES; by FEDER, through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI); by national funds (OE), through FCT/MCTES (POCI-01-0145-FEDER-031268); by the FCT Investigator Programme and Exploratory Project (IF/01634/2015) with financing from the European Social Fund and the Human Potential Operational Programme; by FAPESP (2018/06908-8, 2020/15513-7); and by the CAPES (Coordination of Superior Level Staff Improvement, Brazil), finance code 001.

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  1. CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal

    Daniel Castro, Ana Sofia C. Marques, Mafalda R. Almeida, Mara G. Freire & Ana P. M. Tavares

  2. Department of Engineering Bioprocess and Biotechnology, School of Pharmaceutical Sciences, UNESP - São Paulo State University, Araraquara, Brazil

    Gabriela B. de Paiva, Heitor B. S. Bento, Danielle B. Pedrolli & Valéria C. Santos-Ebinuma

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DC, MRA, MGF, APMT, and VCSE designed and lead the writing process. DC, ASM, GBP, HBSB, DBP, MRA, and VCSE jointly performed the literature search and wrote the manuscript. All authors read and approved the manuscript.

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Castro, D., Marques, A.S.C., Almeida, M.R. et al. L-asparaginase production review: bioprocess design and biochemical characteristics. Appl Microbiol Biotechnol 105, 4515–4534 (2021). https://doi.org/10.1007/s00253-021-11359-y

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