Described are pharmaceutical compositions and medical uses of engineered human arginases, and particularly, among others, a pharmaceutical formulation comprising a protein comprising an amino acid sequence of human Arginase I and a non-native metal cofactor, wherein the non-native metal cofactor is cobalt； a pharmaceutical formulation comprising a human Arginase I protein having a metal binding site and comprising at least one amino acid substitution at the metal binding site, wherein the protein displays an increase in the hydrolysis of Arginine that results in a k cat /K m of at least two fold greater than that of a native human Arginase I； a pharmaceutical formulation comprising a fusion protein comprising any of the said proteins； as well as medical uses related to the above.
