Anticancer Asparaginases: Perspectives in Using Filamentous Fungi as Cell Factories

Pedro Henrique Dias Garcia*, Tales Alexandre Costa-Silva, Martí Morera Gómez, Fabiano Jares Contesini, Paula Renata Bueno Campos Canella, Patrícia de Oliveira Carvalho

*Corresponding author for this work

Research output: Contribution to journalReviewpeer-review

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Abstract

The enzyme L-asparaginase (L-asparagine amidohydrolase) catalyzes the breakdown of L-asparagine into aspartate and ammonia, which leads to an anti-neoplastic activity stemming from its capacity to deplete L-asparagine concentrations in the bloodstream, and it is therefore used in cases of acute lymphoblastic leukemia (ALL) to inhibit malignant cell growth. Nowadays, this anti-cancer enzyme, largely produced by Escherichia coli, is well established on the market. However, E. coli L-asparaginase therapy has side effects such as anaphylaxis, coagulation abnormality, low plasma half-life, hepatotoxicity, pancreatitis, protease action, hyperglycemia, and cerebral dysfunction. This review provides a perspective on the use of filamentous fungi as alternative cell factories for L-asparaginase production. Filamentous fungi, such as various Aspergillus species, have superior protein secretion capacity cCallompared to yeast and bacteria and studies show their potential for the future production of proteins with humanized N-linked glycans. This article explores the past and present applications of this important enzyme and discusses the prospects for using filamentous fungi to produce safe eukaryotic asparaginases with high production yields.
Original languageEnglish
Article number200
JournalCatalysts
Volume13
Issue number1
Number of pages16
ISSN2073-4344
DOIs
Publication statusPublished - 2023

Keywords

  • Cell factory
  • L-asparaginase
  • Filamentous fungi
  • Anti-neoplastic
  • Biopharmaceutical

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