Computational characterization of enzymatic reactive intermediates for the discovery and design of new biocatalytic activities

Posters European Corner 2021

Nom i cognoms / Name and surname
Marc Garcia Borràs

Afiliació / Affiliation
Universitat de Girona, Institut de Química Computacional i Catàlisi (IQCC)

Programa de finançament europeu en que s’enmarca aquest projecte? / European funding programme in which this project is being carried out?
Marie Skłodowska-Curie Schemes

Títol del projecte / Project title
Computational characterization of enzymatic reactive intermediates for the discovery and design of new biocatalytic activities

Número del projecte / Project number
2018 BP 00204

Breu explicació del projecte / Brief explanation of your project
Enzymes are highly efficient biocatalysts, biodegradable, operate under biological conditions, and can offer kcat/kuncat accelerations of several orders of magnitude. However, only few processes have a natural enzyme to accelerate the corresponding chemical reactions. Consequently, the design of new specific enzymes for catalyzing non-natural reactions is highly attractive. Among other strategies, this can be achieved by taking advantage of the intrinsic catalytic promiscuity that natural enzymes exhibit and by introducing specific amino acid changes (i.e. mutations) into their sequences. Catalytic promiscuity refers to the ability of an enzyme to catalyze, in addition to its native function, reactions involving different substrates and that proceed via different transition states and different reaction pathways.

Enzymatic reactive intermediates are species involved in biocatalytic cycles that are not so stable and exhibit short lifetimes. These species are sometimes found to be the source of enzyme catalytic promiscuity, since different potential reaction pathways can diverge from these generated species. Consequently, controlling the behavior of such reactive species could provide a new route to access to new non-natural biocatalytic functions.

In this project new computational protocols to study and characterize reactive intermediates formed over the course of enzyme catalytic pathways will be developed. The new protocol will rely on different multiscale computational approaches that will be combined to account for different factors that interplay key roles on the formation and stabilization of enzymatic reactive intermediates.

Finally, the knowledge acquired will be used to computationally design and engineer new enzyme variants to access to new-to-nature reactions, in a more rational and efficient manner.

Enllaç a la pàgina web del projecte / Link to your project website

Repte en que s’emmarca aquest projecte / Challenge within the framework of this project
Does not apply


Amb el suport de:

Amb el finançament de:

Aquest projecte està cofinançat pel programa de recerca i innovació Horizon Europe de la Unió Europea sota el projecte NitRecerCat (101061189).

This project is co-funded by the European Union’s research and innovation programme Horizon Europe, under the project NitRecercat (101061189).