Predicting an Improvement of Secondary Catalytic Activity of Promiscuos Isochorismate Pyruvate Lyase by Computational Design

摘要

Traditional views on enzymatic activity usually remark on their high efficiency and specificity. However, it has been recently suggested that this paradigm, which has dominated thinking in this field, could be too simplistic. Many enzymes have been found to present secondary catalytic activity or catalytic promiscuity, thus being capable of catalyzing secondary reactions at an active site that was specialized to favor a primary reaction. This promiscuity provides a raw starting point for the evolution of enzymes, as a new duplicated gene presenting low activity would provide a start for adaptative evolution. In fact, new enzymatic functions can evolve in the period of years or even months, as happened recently with new synthetic chemicals or drugs.