Production of L-asparaginase from fungal origin in stable formulation for antileukemic treatment

• Grant number: 19/23620-0
• Support Opportunities: Regular Research Grants
• Duration: January 01, 2021 - December 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Convênio/Acordo: CONFAP - National Council of State Research Support Foundations
• Principal Investigator: Adalberto Pessoa Junior
• Grantee: Adalberto Pessoa Junior
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

L-Asparaginase (ASNase) is a drug of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer, shown higher incidence in children between the second and the fifth year of life, being considered the most common type in children. On an industrial scale, the commercialized enzyme L-asparaginase is of bacterial origin, produced from Escherichia coli and Erwinia chrysanthemi. However, important adverse reactions and toxicity associated with the use of prokaryotic enzyme are observed. Thus, the identification of filamentous fungi producing L-asparaginase with potential pharmaceutical application is important. In this context, the study of the morpho-molecular characterization of the isolate DCFS6 from the Brazilian Savannah soil and the subsequent study of the heterologous production of the enzyme L-asparaginase is fitted. In addition, the Biobetters study, ie drug enhancement through chemical or molecular modifications to the parent product, may reduce the toxicity of the end product, reduce immunogenicity and alter pharmacokinetics and pharmacodynamics, which is of interest in case study. Thus, this project aims to produce, purify, characterize, stabilize and lyophilize, through the cultivation of recombinant E. coli, the heterologous enzyme, and biopharmaceutical, cloned L-asparaginase from the fungus isolated from the Brazilian Savannah soil. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANCHEZ-MOGUEL, IGNACIO; COSTA-SILVA, TALES A.; PILLACA-PULLO, OMAR S.; FLORES-SANTOS, JUAN CARLOS; BARROS FREIRE, ROMINNE KARLA; CARRETERO, GUSTAVO; BUENO, JULIA DA LUZ; CAMACHO-CORDOVA, DAVID I.; SANTOS, JOAO H. P. M.; SETTE, LARA DURAES; et al. Antarctic yeasts as a source of L-asparaginase: Characterization of a glutaminase-activity free L-asparaginase from psychrotolerant yeast Leucosporidium scottii L115. Process Biochemistry, v. 129, p. 12-pg., 2023-03-21. (19/23620-0, 13/19584-2, 13/08617-7)

ANDRADE, KELLEN C. R.; FERNANDES, RILDO A.; PINHO, DANILO BATISTA; DE FREITAS, MARCELA M.; FILHO, EDIVALDO XIMENES FERREIRA; PESSOA, ADALBERTO; SILVA, JOAO INACIO; MAGALHAES, PEROLA O.. Sequencing and characterization of an L-asparaginase gene from a new species of Penicillium section Citrina isolated from Cerrado. SCIENTIFIC REPORTS, v. 11, n. 1, SEP 9 2021. (19/23620-0)