Resurrected Ancestral Proteins as Scaffolds for Protein Engineering

  • Valeria A. Risso
  • Jose M. Sanchez-Ruiz


High stability and enhanced promiscuity (likely linked to conformational flexibility/diversity) contribute to evolvability and are advantageous features in protein scaffolds for laboratory-directed evolution and molecular design. Furthermore, the two features are not necessarily incompatible, and proteins may simultaneously be promiscuous/flexible and highly stable. In fact, it appears plausible that the combination of the two features was not uncommon among the most ancient proteins because (i) ancient life was likely thermophilic and (ii) ancient proteins were likely promiscuous generalists with broad functionalities. Phylogenetic analyses allow the reconstruction of ancestral sequences and provide an approach to explore the properties of ancient proteins. High stability and promiscuity have been often found for proteins encoded by reconstructed ancestral sequences, i.e., for “resurrected” ancestral proteins. The combination of the two features, i.e., the ancestral hyperstable generalist phenotype, has actually been obtained in recent studies. Ancestral protein resurrection thus emerges as a useful source of scaffolds for protein engineering.


Denaturation Temperature Ancestral Sequence Ancient Protein Ancestral Protein Ancestral Reconstruction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Work in the authors’ lab is supported by FEDER Funds and Grants, CSD2009-00088, and BIO2015-66426-R from the Spanish Ministry of Economy and Competitiveness.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Valeria A. Risso
    • 1
  • Jose M. Sanchez-Ruiz
    • 1
  1. 1.Facultad de Ciencias, Departamento de Química FísicaUniversidad de GranadaGranadaSpain

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