TOP: A ribbon-diagram of the TEM-52b-lactamase crystal structure. Arrows show positions of the three mutations that contribute to antibiotic resistance.

BOTTOM: X-axis shows the locations of all the mutations predicted by directed evolution, as well as those found in nature. Y-axis shows the three methods of directed evolution—DNA analogs, gene shuffling, mutator strain—and the natural mutants of b-lactamase that have been identified. Of the eleven mutations predicted by directed evolution, eight (arrows) have been found in nature.

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