The present invention refers to polypeptides with asparaginase activity that have an increased rate of self-processing compared to human wild L-asparaginase (ASRGL1), with mutation in the ASRGL1 glycine rich loop called HGG loop (Histidine 8-Glycine 9-Glycine 10). Polynucleotides that encode the polypeptides of invention are also described here, expression cassettes comprising so-called polynucleotides, expression vectors, host cells, pharmaceutical compositions, uses of the invention polypeptide in the manufacture of a preventive medicine or cancer treatment and methods to produce the polypeptide of invention and to prevent or treat cancer.