Next-generation sequencing (NGS) workflows have several steps, each of which potentially allows for the introduction of errors that could significantly impact the quality and reliability of sequencing results. Reagents and methods used to generate NGS data should therefore be of the highest quality and need to be tested and validated for robust precision and accuracy. Although several reagent options are available for various steps of the NGS workflow, the difference among them exists primarily due to the composition of buffers or the concentration of enzymes. The majority of DNA- and RNA-modifying enzymes used in common NGS reagents belong to “wild-type,” isolated from nature without modification, and these enzymes were never intended as tools for molecular biology. Directed evolution technology selects enzymes used in NGS through a simulated natural selection process in the lab for high performance efficiency.