• Development of biocatalytic carbon-carbon bond formation reactions for the product oriented strategic transformations (CARBOLINK).

    Reference: MINECO (CTQ2015-63563-R)

    CARBOLINK aims to develop suitable C-C bond formation biocatalyst platforms, as key enabling technology (KET) (Industrial Biotechnology) for the selective, green and sustainable production of strategic industrial compounds. Carbon-carbon bond formation is a cornerstone transformation in industrial organic synthesis because complex compounds and key starting materials can be built up from simple molecules. Industrial chemical processes carried out through outdated methodologies usually involve the use of hazardous reactants and consume excessive energy. Biocatalysis performs the chemical transformations of molecules with exquisite selectivity, unparalleled efficacy and under mild conditions, minimizing waste generation and consuming less energy. Biocatalytic C-C bond formation has been successfully used in numerous syntheses, and introduced in the organic chemistry labs as a complement to chemical procedures. However, its industrial utilization remains as a promising, but largely unexplored field due to different hurdles, such as the lack of a broad range of biocatalytic platforms for a broad variety of C-C bond formation methodologies and long development timelines. CARBOLINK will endeavor to tackle those limitations by developing a toolbox of C-C biocatalyst consisting of novel aldolases and variants from structure-guided active site redesign to suit the expected activity. This toolbox will be screened towards selected reactions useful to generate intermediates of industrial APIs (Active Pharmaceutical Ingredients) and other industrial interesting compounds. CARBOLINK expects to develop efficient C-C bond formation biocatalysts (i.e., aldol additions, Michael additions, Stetter reactions and benzoin reactions) for industrial applications and biocatalytic platforms suitable for future developments towards new valuable targets. CARBOLINK expects a Technology Readiness Level (TRL) from TRL2 (i.e. technology concept and application formulated) to TRL4 (i.e., reaction validation in laboratory environment). CARBOLINK is expected to contribute to the sustainability and competitiveness of the Spanish chemical industry by reducing the energy consumption and improving the environmental quality. Altogether, these factors will enhance the welfare and security of the EU citizens.

    Main Investigator: Pere Clapés Saborit

  • Sustainable industrial processes based on a C-C bond-forming enzyme platform (CarbaZymes).

    Reference: H2020-LEIT-BIO-2014-1. Carbazymes-635595.

    The CarbaZymes project will develop the biocatalytic synthesis of 4 APIs and 3 bulk chemicals, representative of market needs in a technical scale and using a broad platform of 4 types of unique C-C bond forming enzymes. Thus CarbaZymes will open the doors to the development of biocatalytic routes for demanded chemicals and gradually pave the way for a more efficient and sustainable chemical industry.

    Main Investigator: Pere Clapés Saborit


  • Redesign of carboligases for the asymmetric carbon-carbon bond formation: towards one-pot multistep synthesis of polyoxygenated compounds (CARBOBIOCAT).

    Reference: MINECO (CTQ2012-31605)

    This project aims at the development of a toolbox of new biocatalyst for the asymmetric carbon-carbon bond formation through aldol addition with broader donor (nucleophile) and acceptor (electrophile) substrate selectivity than those that already exist and with complementary stereochemical outcome. The new biocatalysts will be developed by structure-guided site directed mutagenesis using three existing aldolases as aldol addition biocatalyst platforms, because they have shown to have a great number of synthetic possibilities: D-fructose-6-phosphate aldolase from E. coli (FSA), a alpha-hydroxycarbonyl dependent aldolase, L-rhamnulose-1-phosphate aldolase from E. coli (RhuA) a dihydroxyacetone phosphate (DHAP)-dependent aldolase, and serine hydroxymethyl transferase from Streptococcus thermophilus (SHMTS thermophilus), a glycine-dependent aldolase. The new aldolases will be developed as biocatalyst for: a) one-pot two-consecutive aldol addition reactions towards the synthesis of carbohydrates and analogues (e.g. hexoses, deoxyhexoses, pentoses) from simple prebiotic substrates, b) multistep two-aldol additions for the chemo-enzymatic preparation of polyhydroxylated pipecolic acid derivatives, c) intramolecular aldol addition reactions and, d) the formation of stereogenic quaternary carbons.

    Main Investigator: Pere Clapés Saborit

  • Synthesis of recently reported phase II metabolites for their inclusion in routine doping control analysis.

    Reference: Synthesis of recently reported phase II metabolites for their inclusion in routine doping control analysis. Ref: WADA Research Grant # 12A13OP

    The availability of reference material is crucial in doping control analysis since they are needed both to confirm the presence of an adverse analytical finding and to develop quantitative methods. For this reason, once a new marker for the detection of the misuse of a doping agent has been detected and identified, the chemical synthesis at an adequate scale is required before its inclusion in routine methods.

    Main Investigator: Jesús Joglar

  • Chemo-enzymatic strategies for diversity-oriented synthesis. Cascade biocatalytic aldol additions towards new bioactive compounds. (2010-2012).

    Reference: CTQ2009-07359

    Summary. The goal of this project is to combine the synthetic potential of aldolases (white biotechnology) with organic synthesis to generate new chiral polyhydroxylated compounds, such as iminosugar derivatives. This innovative approach will focus on new molecules more active and selective than those already existing against target enzymes relevant for the treatment and prevention of cancer and hyperglycemia. The combination of biocatalysis and organic chemistry for diversity-oriented synthesis is expected to broaden the scope of methodologies allowing genuinely new and innovative drugs to be discovered with enhanced properties compared to those currently existing. This novel multidisciplinary combination, comprising an essential array of complementary scientific and technological expertise in chemistry and biology, will result in a large increase in relevance and productivity of new molecular entities which will lead to useful outcomes for drug discovery.

    Main Investigator: Pere Clapes Saborit