Proteins carry out most of the molecular tasks of life as we know it, including the catalysis of the large number of life-sustaining biochemical reactions by protein enzymes. Modern proteins have been extensively studied, of course, but they are the outcome of about 4000 million years of evolution on Earth. Therefore, modern proteins are in many cases highly specialized for the molecular tasks in extant (i.e. contemporary) organims and their properties reflect adaptations to modern intra- and extra-cellular enviroments. No doubt, these modern environments differ from the environments that hosted ancestral proteins and, furthermore, it appears plausible that the more ancient proteins were not as highly specialized as modern proteins are. Consequently, the properties of ancestral proteins may have differed substantially from those of their modern counterparts.
For instance, if primordial life thrived in a high temperature envirorment (hydrothermal vents, for instance), we may expect the most ancient proteins to have been highly stable. Also, at the molecular level, a lack of specialization may indicate that the protein is conformationally flexible, with different conformations being responsible for different tasks. These biomolecular features promote evolvability and hypothesized that ancestral proteins should provide excellent scaffolds for the generation of completely new enzymes, a major unsolved problem in protein engineering.
Of course, ancestral proteins belong to extinct organisms and, strictly speaking, do not exist any more. Yet, plausible approximations to their sequences can be derived from phylogenetics and bioinformatics analyses based on suiable models of sequence evolution, in the same manner as words in extinct languages can be reconstructed using suitable models of language evolution. The proteins encoded by the reconstructed sequences can then be prepared in the lab (i.e., “resurrected”) and their properties studied. Ancestral protein resurrection has the capability to yield extreme and useful biomolecular properties when sampling distant sequence space. Accordingly, our contribution to RevoluZion involves the “resurrection” of ancestral protein variants corresponding to modern enzymes with the capability of to degrade plastics. These ancestral forms are expected to display properties that faciliate their practical application in plastic degradation. Furthermore, the ancestral folds should provide suitable scaffolds for enzyme engineering and laboratory evolution efforts aimed at optimizing the plastic degradation capabilities.