Rieske non-heme iron oxygenases (ROs) are a class of dioxygenases that have been used to incorporate molecular oxygen in aromatic compounds for the synthesis of biologically-active products and fine chemicals. Sesquiterpenes and related compounds could also have industrial interest. To date only a few ROs variants have revealed low catalytic activity towards them.
The goal in this project is to rationally design new dioxygenase variants with improved activity towards substrates with sesquiterpene motifs. For that, we propose to apply structural changes in the loops leading to the active-site, as done before.
The methods will include: search for homologous sequences and their modeling, grafting of loops between proteins, calculation of enzyme tunnels, molecular docking, and molecular dynamics. This work should result in candidate variants, of which the most promising ones will be experimentally evaluated for their catalytic properties towards the targeted substrates.