• Aldolases as biocatalyst in asymmetric carbon-carbon bond formation. Synthesis of bioactive molecules

    Our research  is focused on the design, production and evaluation of biocatalysts, particularly aldolases, and biologically active molecules.Chemoenzymatic methodology has the potential to access stereochemically complex molecules that are not easily produced by conventional organic synthesis.Hence, they are particularly appropriate for obtaining new types of structures (i.e. to generate molecular diversity) accessible for investigations in drug discovery.

    Biocatalysts (Aldolases) 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

    The bioactive molecules under investigation are: a) inhibitors of target enzymes involved in cancer and metastasis such as histone deacetylase, fucosidase, fucosiltransferases, sialil transferases, and heparanase, b) the ones whose inhibition may help in the prevention of insulin resistance and elevated blood glucose related to the metabolic syndrome: inhibitors glycogen phosphorilase, alfa- and beta-glucosidases, and intestinal carbohydrate processing enzymes such as sacarase, maltase, isomaltase, threalase, lactase and alfa-amylase.





    Aldol additions mediated by Glycine aldolases.

    KEYWORDS: biocatalysis, protein engineering, glycosidases, glycosyltransferases, inhibitors, glycoprocessing enzymes, organic synthesis, chemoenzymatic synthesis, enzyme and ligand design, dihydroxyacetone (DHAP) dependent aldolases, Glycine dependent aldolases.