Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, disclosed are modified cystathionine-γ-lyases comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, compositions and methods are provided for the treatment of cancer and cystinuria using the disclosed modified enzymes or nucleic acids encoding said enzymes.
