Molecular engineering of the L-tryptophan-depleting enzyme indolyl-3-alkane alpha-hydroxylase.

Polymaleic acid and polyacrylic acid polymers have been covalently linked to indolyl-3-alkane alpha-hydroxylase with a shift of the pH optimum from 3.5 to between 5.0 and 5.5. In addition, the specific activity of the modified enzyme was increased approximately threefold at pH 7.0. The Km values of the polymer-bound enzyme preparations are essentially the same as that of the native enzyme. The plasma half-life was shortened from 6-7 hours with the native enzyme to 2-4 hours with the modified enzymes. The degree of L-tryptophan depletion in the circulation of mice, however, was the same during a 24-hour period after injection of native or modified enzymes.