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Therapeutic l-asparaginase: upstream, downstream and beyond
André Moreni Lopes1, Laura de Oliveira-Nascimento2, Artur Ribeiro3
1a Department of Biochemical and Pharmaceutical Technology , School of Pharmaceutical Sciences, University of São Paulo , São Paulo , Brazil.
Critical Reviews in Biotechnology
|December 24, 2015
Summary
Microbial l-asparaginase (ASNase) is a cost-effective antitumor agent for leukemia. Enhancing its production and therapeutic profile through protein engineering and new sources is crucial for better cancer treatment outcomes.
Area of Science:
- Biochemistry
- Enzymology
- Cancer Therapeutics
Background:
- L-asparaginase (ASNase) is an established antitumor enzyme used in treating acute lymphoblastic leukemia and lymphosarcoma.
- It functions by hydrolyzing l-asparagine, leading to cytotoxicity in leukemic cells.
- Microbial production of ASNase is favored for its cost-effectiveness and environmental benefits.
Purpose of the Study:
- To provide a comprehensive review of microbial l-asparaginase (ASNase) production.
- To discuss various aspects including microbial sources, production conditions, protein engineering, and downstream processing.
- To highlight challenges and future directions for improving ASNase efficacy and safety in cancer therapy.
Main Methods:
- Review of existing literature on microbial ASNase production.
- Analysis of biochemical characteristics, stability, bioavailability, toxicity, and allergenicity.
- Exploration of protein engineering strategies and recombinant production methods.
Main Results:
- Microbial ASNase production is a viable and eco-friendly alternative.
- Key factors influencing enzyme production and characteristics have been identified.
- Protein engineering and exploring new sources are vital for therapeutic advancement.
Conclusions:
- Further research into novel microbial sources and protein engineering is necessary to enhance ASNase availability and therapeutic potential.
- Optimizing production and purification processes can lead to improved drug efficacy and reduced side effects.
- Addressing pharmacokinetic and toxicological profiles is essential for advancing ASNase in cancer treatment.
Keywords:
Acute lymphoblastic leukemiaantineoplastic activitybiopharmaceuticall-asparaginasemicrobial l-asparaginase productionMore Related Videos
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