Glutaminase-free L-asparaginase production by Leucosporidium muscorum isolated from Antarctic marine-sediment

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....

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Bibliographic Details
Published in:Preparative Biochemistry & Biotechnology
Main Authors: Freire, Rominne Karla Barros, Mendonça, Carlos Miguel Nóbrega, Ferraro, Rafael Bertelli, Moguel, Ignacio Sánchez, Tonso, Aldo, Lourenço, Felipe Rebello, Santos, João Henrique Picado Madalena, Sette, Lara Durães, Pessoa Junior, Adalberto
Other Authors: Universidade Estadual Paulista (UNESP)
Format: Article in Journal/Newspaper
Language:English
Published: 2020
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Online Access:http://hdl.handle.net/11449/202103
https://doi.org/10.1080/10826068.2020.1815053
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Summary: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 muscorum CRM 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 °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.