L-Asparaginase from Penicillium sizovae Produced by a Recombinant Komagataella phaffii Strain

Marcela Freitas, Paula Souza, Mauricio Homen de Mello, Yris M. Fonseca-Bazzo, Damaris Silveira, Edivaldo X. Ferreira Filho, Adalberto Pessoa Junior, Dipak Sarker, David Timson, Joao Inacio Silva, Perola O. Magalhaes

Research output: Contribution to journalArticlepeer-review


L-asparaginase is an important enzyme in the pharmaceutical field used as treatment for acute lymphoblastic leukemia due to its ability to hydrolyze L-asparagine, an essential amino acid synthesized by normal cells, but not by neoplastic cells. Adverse effects of L-asparaginase formulations are associated with its glutaminase activity and bacterial origin; therefore, it is important
to find new sources of L-asparaginase produced by eukaryotic microorganisms with low glutaminase activity. This work aimed to identify the L-asparaginase gene sequence from Penicillium sizovae, a filamentous fungus isolated from the Brazilian Savanna (Cerrado) soil with low glutaminase activity, and to biosynthesize higher yields of this enzyme in the yeast Komagataella phaffii. The L-asparaginase gene sequence of P. sizovae was identified by homology to L-asparaginases from species of Penicillium of the section Citrina: P. citrinum and P. steckii. Partial L-asparaginase from P. sizovae, lacking the periplasmic signaling sequence, was cloned, and expressed intracellularly with highest enzymatic activity achieved by a MUT+ clone cultured in BMM expression medium; a value 5-fold greater than that obtained by native L-asparaginase in P. sizovae cells. To the best of our knowledge, this is the first literature report of the heterologous production of an L-asparaginase from a filamentous fungus by a yeast.
Original languageEnglish
Article number746
Number of pages17
Issue number6
Publication statusPublished - 14 Jun 2022

Bibliographical note

Funding Information:
Funding: This research was partially funded by the Rising Stars Initiative, University of Brighton, United Kingdom; by the Higher Education Personnel Improvement Coordination (CAPES) [Finance Code 001] and the Foundation for Research Support of the Federal District (FAP-DF) [process numbers 193.001.661/2017, 0193.001797/2017 and 193.0000.919/2020-07].

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Asparginase
  • Penicillium


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