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This striking distinction between the WT BoNT/E and D3 starting points is consistent with our findings from the three substrate variant evolutions, and strongly suggests that starting point redesign expands the productive mutation space of an evolving enzyme, enabling the emergence of new genotypes with virtually absolute specificity reprogramming not attained by evolving the natural enzyme

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Exclusion criteria: Patients with acute viral hepatitis, immune hepatitis, Wilson disease , concurrent conditions in which free radical production is elevated like other inflammatory processes outside the liver or intake of antioxidant drugs affecting free radical scavenging such as vitamin C, A and E at time of biopsy