How do enzymes evolve?

evolvability

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.

Just published

  • Elias M, Wieczorek G, Rosenne S, Tawfik DS. "The universality of enzymatic rate-temperature dependency." Trends in Biochemical Sciences 2014 Jan.

  • Cherny I, Greisen P Jr, Ashani Y, Khare SD, Oberdorfer G, Leader H, Baker D, Tawfik DS. "Engineering V-type nerve agents detoxifying enzymes using computationally focused libraries." Chemical Biology 2013 Nov 15.

  • Rockah-Shmuel L, Tóth-Petróczy Á, Sela A, Wurtzel O, Sorek R, Tawfik DS. "Correlated occurrence and bypass of frame-shifting insertion-deletions (InDels) to give functional proteins." Plos Genetics 2013 Oct 24.

  • Wellner A, Gurevich MR, Tawfik DS. “Mechanisms of protein sequence divergence and incompatibility.” Plos Genetics 2013 July.