Serine protease Jurassic Park

Wouters et al. inferred ancestral sequences from parsimony analysis of a multiple alignment of 56 immune defense protease (IDP) sequences and constructed a synthetic gene to express the recombinant protein that they called Stemzyme-IDP-β. Using angiotensin II as substrate for kinetic and binding studies, the authors observed high catalytic efficiency and broad substrate specificity and a tolerance to mutation at the binding site, with different mutations resulting in activities similar to some of the synthetic enzyme's descendents. They suggest that a form of reverse evolution must have occurred that provided a mechanism for enzymes with narrow specificity to evolve from enzymes with already narrow specificity."Our findings... suggest that once a narrow primary specificity had become established, the further generation of diversity required a reversion to the presumed original state. That is, despecialization or evolution-in-reverse was required for further diversification," the authors conclude.