Engineering a de Novo Transport Tunnel

Here we describe the computational design and directed evolution of a de novo transport tunnel in a haloalkane dehalogenase. Mutants with a blocked native tunnel and a newly opened auxiliary tunnel in a distinct part of the structure showed dramatically modified properties. The mutants with blocked tunnels acquired specificity never observed with native family members: up to 32 times increased substrate inhibition and 17 times reduced catalytic rates. Opening of the auxiliary tunnel resulted in specificity and substrate inhibition similar to those of the native enzyme and the most proficient haloalkane dehalogenase reported to date.

de_novo_tunnel

Brezovsky, J., Babkova, P., Degtjarik, O., Fortova, A., Gora, A., Iermak, I., Rezacova, P., Dvorak, P., Kuta Smatanova, I., Prokop, Z., Chaloupkova, R., Damborsky, J., 2016: Engineering a de Novo Transport Tunnel. ACS Catalysis 6: 7597-7610.

Ondrej Vavra celebrating success with his presentation on CaverDock
Lecture by Dr. Stavrakis from ETH Zurich
High evaluation of the team’s research performance
Klaudia Chmelova and Veronika Liskova passed doctoral state exam
ELIXIR CZ annual conference 15 – 16 Nov, 2017
New video explaining the goals of Rafts4Biotech EU project
Invitation to a presentation by Synthetic Genomics