Engineering of the signal secretory portion of asparaginase from Saccharomyces cerevisiae for extracellular biopharmaceutical production

• Grant number: 16/09138-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2016
• Effective date (End): January 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal researcher: Gisele Monteiro
• Grantee: Henrique Pellin Biasoto
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical, AP.TEM

Abstract

L-asparaginase, discovered in 1953 by Kidd is an effective inhibitor of tumor growth, used in chemotherapy sessions in order to exhaust the asparagine (Asn) and glutamine (Gln) stock, only needed for tumor cell Lymphoblastic Leukemia (LLA). Despite being an efficient antileukemic, the high cost of production of L-asparaginase and the low demand of the international market for the native enzyme from Escherichia coli resulted in the interruption of their trade in the Brazilian market, which is dependent on imports. This shortage led us to generate technical knowledge to start production of this biopharmaceutical drug in the national territory; for that we propose to study different extracellular signaling sequences in a recombinant L-asparaginase in Pichia pastoris. Furthermore, serious immunogenic effects of treatment with the E. coli enzyme has led us to seek other sources of L-asparaginase. So we chose the L-asparaginase II enzyme of S. cerevisiae with antileukemic potential and currently studied in our laboratory.