Pere Clapés Research blog

Biotransformation & Bioactive Molecules Research Group

Research

Aldolases as biocatalyst in asymmetric carbon-carbon bond formation

The research of our group is focused on the development and optimization of new and existing biocatalyst for carbon-carbon bond formation (carboligases). Carboligases have the potential to efficiently access complex molecular scaffolds from simple starting materials, with unparalleled stereoselectivity and without a need for tedious and time-consuming iterative steps for protection and deprotection of sensitive or reactive functional groups. Three goals are pursued: first to develop new cost-efficient and eco-friendly process for the chemical manufacturing industry, second to produce new compounds (i.e. new structure types generating molecular diversity) accessible for investigations in drug discovery and third to engineer the biocatalyst for improving its substrate tolerance, stereoselectivity, and catalytic properties (i.e. towards non-natural reactions) to broaden its window of applicability. The research includes computational models for ligand-protein interaction essential for biocatalyst optimization by structure-guided protein engineering.

 

Carboligases are fundamental components of the chemoenzymatic methodology. Our research includes screening, production by fermentative process of overexpressed recombinant strains, their evaluation as a biocatalyst in target organic reactions and their redesign to alter the activity and selectivity.

Computational models for ligand-protein interactions as a way to redesign or modify rationally the biocatalysts and the biologically active molecules of interest are of paramount importance.

Fuculose 1-phosphate aldolase active site

Molecules synthesized using carboligases includes: iminosugars, carbohydrates, deoxysugars derivatives and analogues .

Aldol additions mediated by Glycine aldolases

KEYWORDS: biocatalysis, protein engineering,  organic synthesis, chemoenzymatic synthesis, enzyme and ligand design, dihydroxyacetone phosphate (DHAP) dependent aldolases, Glycine aldolases and related enzymes, Pyruvate aldolases and related enzymes, D-fructose-6-phosphate aldolase (FSA).

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