Acute lymphoblastic leukemia (ALL) is characterized by the uncontrolled production of lymphoid blasts and by blocking the production of normal hematopoiesis, and neoplasia is more frequent in children and adolescents. Treatment of the disease is done with L-asparaginase (L-ASNase), an enzyme obtained from the bacteria Escherichia coli and Dickeya chrysanthemi (formerly known as Erwinia chrysanthemi). L-ASNase hydrolyzes L-asparagine (Asn) in aspartic acid (Asp) and ammonia and prevents tumor cells from obtaining Asn from the bloodstream for protein synthesis and proliferation, leading to cell death by apoptosis. Since the 1970s the enzyme has been the main agent for the remission of ALL. However, both formulations are associated with a high rate of adverse effects, mainly drug resistance caused by the production of anti-asparaginase antibodies and marked hypersensitivity, which compromise the efficacy of the treatment. In addition, patients suffer from various periods of drug shortage on the world market; Here in Brazil the lack of commercialization occurs since 2013. This way it is necessary to search for new alternatives for the treatment of ALL. The development of mutant isoforms from commercially available bacterial enzymes may contribute to the reduction of adverse effects and be an alternative for national marketing. Our research group using the L-ASNase from D. chrysanthemi has created a library of mutants from random mutagenesis. From this library, ten mutants were selected that presented in preliminary tests an improvement in the specific activity of up to 285% in relation and wild enzyme. This project aims to characterize the ten isoforms of D. chrysanthemi and to select those that present the best biochemical characteristics to evaluate the cytotoxic potential.
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