Biochemical characteristics and antitumor activity of the recombinant protein L-asparaginase I small

Abstract

A significant number of patients with acute leukemia of lymphocytic (ALL), malignant cells have a metabolic defect in the synthesis of asparagine (Asn), depending on an exogenous source of this amino acid to survive. The enzyme L-asparaginase is used in the treatment of this disease in order to exhaust the stocks of asparagine in the bloodstream required for tumor cells. Although this enzyme is effective in inducing remissions, asparaginase preparations commercially available obtained from Escherichia coli and Erwinia chrysanthemi have high levels of adverse effects, such as hypersensitivity and allergic reactions. Given the severe immunogenic effects of treatment with these formulations, there is a search for alternative sources of asparaginase. Saccharomyces cerevisiae shows the ASP1 gene, which encode L-asparaginase I (ScASNaseI). Recently, L-asparaginase of S. cerevisiae has been successfully expressed in E. coli. However, high molecular weight protein complexes of fused protein with histidine tail were obtained, which after processing for His-tail removal resulted in a low molar mass monomer enzyme called small. Due to its relatively small size (45kDa), L-asparaginase I small (ScASNaseI small) may have low immunogenicity, possessing high potential for pharmaceutical application in the treatment of ALL. Although we know some characteristics of this recombinant monomeric protein, we do not know whether this can be obtained directly if it is not fused to the histidine tail and processed. In this work, we will evaluate the expression of the native protein (without any fusion tail) in E. coli and we will discuss the biochemical characteristics and antitumor activity of the recombinant protein L-asparaginase I small. (AU)