Título :	L-Asparaginase from Penicillium sizovae produced by a recombinant Komagataella phaffii strain
Autor :	Freitas, Marcela Medeiros de Souza, Paula Monteiro de Homem de Mello, Mauricio Fonseca-Bazzo, Yris Maria Silveira, Dâmaris Ferreira Filho, Edivaldo Ximenes Pessoa Junior, Adalberto Sarker, Dipak Timson, David Inácio, João Magalhães, Pérola de Oliveira
metadata.dc.identifier.orcid:	https://orcid.org/0000-0002-6112-9903 https://orcid.org/0000-0003-1824-2211 https://orcid.org/0000-0002-4541-9177 https://orcid.org/0000-0002-1230-3207 https://orcid.org/0000-0003-1851-5224 https://orcid.org/0000-0003-4947-8753 https://orcid.org/0000-0002-5268-8690 https://orcid.org/0000-0002-2912-415X https://orcid.org/0000-0002-0985-8818 https://orcid.org/0000-0001-8011-6940
metadata.dc.contributor.affiliation:	University of Brasilia, Health Sciences School University of Brasilia, Health Sciences School University of Brasilia, Health Sciences School University of Brasilia, Health Sciences School University of Brasilia, Health Sciences School University of Brasilia, Institute of Biological Sciences University of Sao Paulo, Department of Biochemical and Pharmaceutical Technology University of Brighton, School of Pharmacy and Biomolecular Sciences University of Brighton, School of Pharmacy and Biomolecular Sciences University of Brighton, School of Pharmacy and Biomolecular Sciences University of Brasilia, Health Sciences School
Assunto::	L-Asparaginase Leucemia linfoblástica aguda (LLA) Clonagem Fungos
Fecha de publicación :	14-jun-2022
Editorial :	MDPI
Citación :	FREITAS, Marcela et al. L-Asparaginase from Penicillium sizovae produced by a recombinant Komagataella phaffii strain. Pharmaceuticals, [S. l.], v. 15, n.6, 2022. DOI: https://doi.org/10.3390/ph15060746.
Abstract:	: 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.
metadata.dc.description.unidade:	Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR) Instituto de Ciências Biológicas (IB) Departamento de Biologia Celular (IB CEL)
metadata.dc.description.ppg:	Programa de Pós-Graduação em Ciências Farmacêuticas
DOI:	https://doi.org/10.3390/ph15060746
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