How do enzymes evolve?


Our research is aimed at understanding how proteins, and enzymes in particular, perform their function, and how they evolve. The scientific activities lie at the interface of Chemistry and Biology. We combine molecular biology, organic chemistry, and state-of-the-art high-throughput screening technologies, towards the generation of new proteins with tailor-made properties. We perform mechanistic, kinetic and structural studies, in order to understand the mechanism of action of our newly-evolved proteins, and of natural proteins.

How do proteins evolve? Natural selection is yielding molecular machines with breath-taking performances, e.g., enzymes that accelerate the rate of chemical transformations by factors of 106 up to 1017. Strikingly, new functions can evolve within years or even months, as happens with drug resistance, and with enzymes that degrade man-made chemicals. Why is this process, which is based on ‘trial and error’ so rapid and efficient? We largely lack the fossils of the protein world, but we can reproduce protein evolution in the laboratory and in real time, implementing the principles of Darwinian evolution to individual genes and enzymes. In this way we can get a glimpse of the evolutionary intermediates, routes, and mechanisms, that may have led the way to the highly proficient enzymes known to us today.

The ability to evolve proteins in the laboratory is also a powerful mean of engineering novel tailor-made enzymes for a range of applications including the detoxification of organophosphates and arteriosclerosis.

A "lab review" by Tyler Hampton.

Just published

  • Bar-Rogovsky H, Stern A, Penn O, Kobl I, Pupko T, Tawfik DS. "Assessing the prediction fidelity of ancestral reconstruction by a library approach." Protein Eng Des Sel. 2015 Aug 13.

  • Rockah-Shmuel L, Tóth-Petróczy Á, Tawfik DS. "Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations." PLoS Comput Biol. 2015 Aug 14.

  • Yanagida H, Gispan A, Kadouri N, Rozen S, Sharon M, Barkai N, Tawfik DS. "The Evolutionary Potential of Phenotypic Mutations." PLoS Genet. 2015 Aug 5.

  • Alcolombri U, Ben-Dor S, Feldmesser E, Levin Y, Tawfik DS, Vardi A. "MARINE SULFUR CYCLE. Identification of the algal dimethyl sulfide-releasing enzyme: A missing link in the marine sulfur cycle." Science 2015 Jun 26.