Glutaminase-free L-asparaginase production byLeucosporidium muscorumisolated from Antarctic marine-sediment

Author(s)

Freire, Rominne Karla Barros ^[1] ; Mendonca, Carlos Miguel Nobrega ^[1] ; Ferraro, Rafael Bertelli ^[1] ; Moguel, Ignacio Sanchez ^[1] ; Tonso, Aldo ^[2] ; Lourenco, Felipe Rebello ^[3] ; Santos, Joao Henrique Picado Madalena ^[1] ; Sette, Lara Duraes ^[4] ; Pessoa Junior, Adalberto ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Biochem & Pharmaceut Technol, Sch Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Polytech Sch, Dept Chem Engn, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, Sao Paulo - Brazil

^[4] State Univ Julio de Mesquita Filho UNESP, Inst Biosci, Dept Gen & Appl Biol, Rio Claro - Brazil

• Document type: Journal article
• Source: PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY; v. 51, n. 3 SEP 2020.
• Web of Science Citations: 0

Abstract

L-asparaginase (ASNase) is an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Commercial bacterial ASNases increase patient survival, but the consequent immunological reactions remain a challenge. Yeasts ASNase is closer to human congeners and could lead to lower side effects. Among 134 yeast strains isolated from marine-sediments in King George Island, Antarctica, nine were L-asparaginase producing yeasts and glutaminase-free.Leucosporidium muscorumCRM 1648 yielded the highest ASNase activity (490.41 U.L-1) and volumetric productivity (5.12 U.L(-1)h(-1)). Sucrose, yeast extract and proline were the best carbon and nitrogen sources to support growth and ASNase production. A full factorial design analysis pointed the optimum media condition for yeast growth and ASNase yield: 20 g L(-1)sucrose, 15 g L(-1)yeast extract and 20 g L(-1)proline, which resulted in 4582.5 U L(-1)and 63.64 U L(-1)h(-1)of ASNase and volumetric productivity, respectively. Analysis of temperature, pH, inoculum and addition of seawater indicated the best condition for ASNase production by this yeast: 12-15 degrees C, pH 5.5-6.5 and seawater >25% (v/v). Inoculum concentration seems not to interfere. This work is pioneer on the production of ASNase by cold-adapted yeasts, highlighting the potential of these microbial resources as a source of glutaminase-free L-asparaginase for commercial purposes. (AU)

• FAPESP's process: 18/25994-2 - Development of novel platforms for PEGylation of proteins with therapeutic potential using microfluidics
• Grantee: João Henrique Picado Madalena Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical
• Grantee: Adalberto Pessoa Junior
• Support Opportunities: Research Projects - Thematic Grants