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Recombinant L-Asparaginase from Zymomonas mobilis: A Potential New Antileukemic Agent Produced in Escherichia coli

2016; Public Library of Science; Volume: 11; Issue: 6 Linguagem: Inglês

10.1371/journal.pone.0156692

1932-6203

Karen Einsfeldt, Isis Cavalcante Baptista, Joana C. Castanheira, Isabele Campos Costa‐Amaral, Elaine Sobral da Costa, Maria Cecília Menks Ribeiro, Marcelo Gerardin Poirot Land, Tito Lívio Moitinho Alves, Ariane Leites Larentis, Rodrigo Volcan Almeida,

DNA Repair Mechanisms

L-asparaginase is an enzyme used as a chemotherapeutic agent, mainly for treating acute lymphoblastic leukemia. In this study, the gene of L-asparaginase from Zymomonas mobilis was cloned in pET vectors, fused to a histidine tag, and had its codons optimized. The L-asparaginase was expressed extracellularly and intracellularly (cytoplasmically) in Escherichia coli in far larger quantities than obtained from the microorganism of origin, and sufficient for initial cytotoxicity tests on leukemic cells. The in silico analysis of the protein from Z. mobilis indicated the presence of a signal peptide in the sequence, as well as high identity to other sequences of L-asparaginases with antileukemic activity. The protein was expressed in a bioreactor with a complex culture medium, yielding 0.13 IU/mL extracellular L-asparaginase and 3.6 IU/mL intracellular L-asparaginase after 4 h of induction with IPTG. The cytotoxicity results suggest that recombinant L-asparaginase from Z. mobilis expressed extracellularly in E.coli has a cytotoxic and cytostatic effect on leukemic cells.