BIOTRANSFORMATION AND BIOACTIVE MOLECULES
Group Leader: Pere Clapés
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:
- to develop new cost-efficient and eco-friendly process for the chemical manufacturing
- to produce new compounds (i.e. new structure types generating molecular diversity) accessible for investigations in drug discovery
- 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.
Personal web: https://pereclapes.wordpress.com/
- Carboligases as biocatalyst in asymmetric carbon-carbon bond formation. 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.
- Artificial carboligases and xenocarboligases constructed by chemical modification of proteins with artificial cofactors or protein engineering by introduction of conveniently functionalized non-coded amino acids (ncAA) bearing secondary and tertiary amines using the stop codon suppression (SCS) approach.
- 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.
- Molecules synthesized using carboligases includes: iminosugars, carbohydrates, deoxysugars, derivatives, ketoacids, amino acids and analogues.
KEYWORDS: biocatalysis, protein engineering, organic synthesis, chemoenzymatic synthesis, enzyme and ligand aldolases: dihydroxyacetone (DHA) utilizing aldolases, dihydroxyacetonephosphate (DHAP)-dependent aldolases, glycine aldolases and related enzymes, pyruvate aldolases and related enzymes.
Scientific staff
Pere Clapés
Research Professor
pere.clapes@iqac.csic.es
Jesús Joglar
Tenured Scientist
jesus.joglar@iqac.csic.es
Jordi Bujons
Tenured Scientist
jordi.bujons@iqac.csic.es
Lab people
Karel Hernández
Postdoctoral Researcher
karel.hernandez@iqac.csic.es
Carlos José Moreno
Predoctoral Researcher
carlos.moreno@iqac.csic.es
Saurabh Ahirwar
Predoctoral Researcher
saurabh.ahirwar@iqac.csic.es
- Three-Component Stereoselective Enzymatic Synthesis of Amino-Diols and Amino-Polyols
Ford, G.J., Swanson, C.R., Bradshaw Allen, R.T., Marshall, J.R., Mattey, A.P., Turner, N.J., Clapés, P., Flitsch, S.L.
Journal of the American Chemical Society, 2022
- Cloning, expression, and one-step purification/immobilization of two carbohydrate-binding module-tagged alcohol dehydrogenases
Benito, M., Román, R., Ortiz, G., Casablancas, A., Álvaro, G., Caminal, G., González, G., Guillén, M.
Journal of Biological Engineering, 16 (1), art. no. 16, 2022
- Process intensification at the expression system level for the production of 1-phosphate aldolase in antibiotic-free E. coli fed-batch cultures
Pasini, M., Fernández-Castané, A., Caminal, G., Overton, T.W., Ferrer, P.
Journal of Industrial Microbiology and Biotechnology, 49 (4), art. no. kuac018, 2022
- Comparison between two reactors using Trametes versicolor for agricultural wastewater treatment under non-sterile condition in sequencing batch mode
Hu, K., Sarrà, M., Caminal, G.
Journal of Environmental Management, 293, art. no. 112859, 2021
- Synthesis of a precursor of D-fagomine by immobilized fructose-6-phosphate aldolase
Masdeu, G., Vázquez, L.M., López-Santín, J., Caminal, G., Kralj, S., Makovec, D., Álvaro, G.,Guillén, M.
PLoS ONE, 16 (4 April 2021), art. no. e0250513, 2021 - Fungal degradation of selected medium to highly polar pesticides by Trametes versicolor: kinetics, biodegradation pathways, and ecotoxicity of treated waters
Hu, K., Barbieri, M.V., López-García, E., Postigo, C., López de Alda, M., Caminal, G., Sarrà, M.
Analytical and Bioanalytical Chemistry, 414 (1), pp. 439-449. 2022
- Thermostability Engineering of a Class II Pyruvate Aldolase from Escherichia coli by in Vivo Folding Interference
Sandra Bosch, Esther Sanchez-Freire, María Luisa del Pozo, Morana C̆esnik, Jaime Quesada, Diana M. Mate, Karel Hernández, Yuyin Qi, Pere Clapés, Đurđa Vasić-Rački, Zvjezdana Findrik Blažević, José Berenguer, and Aurelio Hidalgo
ACS Sustainable Chem. Eng. 2021, 9, 15, 5430–5436
- Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition-Transamination Reactions
Moreno, C.J., Hernández, K., Charnok, S.J., Gittings, S., Bolte, M., Joglar, J., Bujons, J., Parella, T., Clapés, P.
ACS Catalysis, pp. 4660-4669. 2021
- Chemoenzymatic Production of Enantiocomplementary 2-Substituted 3-Hydroxycarboxylic Acids from l-α-Amino Acids
Pickl, M., Marín-Valls, R., Joglar, J., Bujons, J., Clapés, P.
Advanced Synthesis and Catalysis, 363 (11), pp. 2866-2876. 2021
- A cascade reaction for the synthesis of D-fagomine precursor revisited: Kinetic insight and understanding of the system
Sudar, M., Česnik, M., Clapés, P., Pohl, M., Vasić-Rački, Đ., Findrik Blažević, Z.
New Biotechnology, 63, pp. 19-28. 2021
- An innovative route for the production of atorvastatin side-chain precursor by DERA-catalysed double aldol addition
Švarc, A., Fekete, M., Hernandez, K., Clapés, P., Findrik Blažević, Z., Szekrenyi, A., Skendrović, D., Vasić-Rački, Đ., Charnock, S.J., Presečki, A.V.
Chemical Engineering Science, art. no. 116312, 2021
- Prospects on coupling UV/H2O2 with activated sludge or a fungal treatment for the removal of pharmaceutically active compounds in real hospital wastewater
Mir-Tutusaus, J.A., Jaén-Gil, A., Barceló, D., Buttiglieri, G., Gonzalez-Olmos, R., Rodriguez-Mozaz, S., Caminal, G., Sarrà, M.
Science of the Total Environment, 773, art. no. 145374, 2021
- Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes
Roser Marín-Valls, Karel Hernández, Michael Bolte, Teodor Parella, Jesús Joglar, Jordi Bujons, and Pere Clapés
J. Am. Chem. Soc. Journal of the American Chemical Society, 142 (46), pp. 19754-19762, 2020
- Remediation of bentazone contaminated water by Trametes versicolor: Characterization, identification of transformation products, and implementation in a trickle-bed reactor under non-sterile conditions
García-Vara, M., Hu, K., Postigo, C., Olmo, L., Caminal, G., Sarrà, M., López de Alda, M.
Journal of Hazardous Materials, art. no. 124476, 2020
- Live-Cell-Templated Dynamic Combinatorial Chemistry
Carbajo, D., Pérez, Y., Bujons, J., Alfonso, I.
Angewandte Chemie - International Edition, 2020.
- Live‐Cell‐Templated Dynamic Combinatorial Chemistry
Daniel Carbajo, Yolanda Pérez, Jordi Bujons, Ignacio Alfonso
Angew. Chem. Int. Ed.. doi:10.1002/anie.202004745
- Convergent in situ Generation of Both Transketolase Substrates via Transaminase and Aldolase Reactions for Sequential One‐Pot, Three‐Step Cascade Synthesis of Ketoses
Lorillière, M.; Guérard-Hélaine, C.; Gefflaut, T.; Fessner, W.-D.; Clapés, P.; Charmantray, F.; Hecquet, L.
ChemCatChem 2020, 12, 812-817.
- Cascade enzymatic synthesis of l-homoserine – mathematical modelling as a tool for process optimisation and design
Česnik, M., Sudar, M., Hernández, K., Charnock, S., Vasić-Rački, D., Clapés, P., Findrik Blažević, Z.
Reaction Chemistry and Engineering, 5 (4), pp. 747-759. 2020
- Model-based optimization of the enzymatic aldol addition of propanal to formaldehyde: A first step towards enzymatic synthesis of 3-hydroxybutyric acid
Česnik, M., Sudar, M., Roldan, R., Hernandez, K., Parella, T., Clapés, P., Charnock, S., Vasić-Rački, Findrik Blažević, Z.
Chemical Engineering Research and Design, 150, pp. 140-152. 2019
- Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation
Marín-Valls, R., Hernández, K., Bolte, M., Joglar, J., Bujons, J., Clapés, P.
ACS Catalysis, 9 (8), pp. 7568-7577. 2019
- Identification of benzo[cd]indol-2(1H)-ones as novel Atg4B inhibitors via a structure-based virtual screening and a novel AlphaScreen assay
Quintana, M., Bilbao, A., Comas-Barceló, J., Bujons, J., Triola, G.
European Journal of Medicinal Chemistry, 178, pp. 648-666. 2019
- Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes
Roldán, R., Hernández, K., Joglar, J., Bujons, J., Parella, T., Fessner, W.-D., Clapés, P.
Advanced Synthesis and Catalysis, 2019
- Reactor and microreactor performance and kinetics of the aldol addition of dihydroxyacetone to benzyloxycarbonyl-N-3-aminopropanal catalyzed by D-fructose-6-phosphate aldolase variant A129G
Sudar, M., Findrik, Z., Szekrenyi, A., Clapés, P., Vasić-Rački, Đ.
Chemical Engineering Communications, 206 (7), pp. 927-939. 2019
- Determination of the β-glycosylate fraction of contaminants of emerging concern in lettuce (Lactuca sativa L.) grown under controlled conditions
Hurtado, C., Domínguez, C., Clapés, P., Bayona, J.M.
Anal Bioanal Chem 2018, 410 (23), 5715-5721.
- Biocatalytic Aldol Addition of Simple Aliphatic Nucleophiles to Hydroxyaldehydes
Roldán, R., Hernandez, K., Joglar, J., Bujons, J., Parella, T., Sánchez-Moreno, I., Hélaine, V., Lemaire, M., Guérard-Hélaine, C., Fessner, W.-D., Clapés, P.
ACS Catalysis, 8 (9), pp. 8804-8809. 2018
- Intramolecular Benzoin Reaction Catalyzed by Benzaldehyde Lyase from Pseudomonas Fluorescens Biovar
Hernández, K.; Parella, T.; Petrillo, G.; Usón, I.; Wandtke, C. M.; Joglar, J.; Bujons, J.; Clapés, P.
Angew. Chem. Int. Ed. 2017, 56 (19), 5304-5307
- 2-Keto-3-Deoxy-L-Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives.
Hernández, K.; Gómez, A.; Joglar, J.; Bujons, J.; Parella, T.; Clapés, P.
Adv. Synth. Catal. 2017, 359 (12), 2090-2100.
- Combining Aldolases and Transaminases for the Synthesis of 2-Amino-4-hydroxybutanoic Acid.
Hernandez, K.; Bujons, J.; Joglar, J.; Charnock, S. J.; Domínguez de María, P.; Fessner, W. D.; Clapés, P.
ACS Catal. 2017, 7, 1707-1711.
- Asymmetric assembly of aldose carbohydrates from formaldehyde and glycolaldehyde by tandem biocatalytic aldol reactions.
Szekrenyi, A.; Garrabou, X.; Parella, T.; Joglar, J.; Bujons, J.; Clapés, P.
Nat. Chem. 2015, 7 (9), 724-729.
- Minimalist Protein Engineering of an Aldolase Provokes Unprecedented Substrate Promiscuity.
Güclü, D.; Szekrenyi, A.; Garrabou, X.; Kickstein, M.; Junker, S.; Clapés, P.; Fessner, W.-D.
ACS Catal. 2016, 6, 1848-1852.
- Structure-Guided Engineering of D-Fructose-6-Phosphate Aldolase for Improved Acceptor Tolerance in Biocatalytic Aldol Additions
Soler, A.; Gutiérrez, M. L.; Bujons, J.; Parella, T.; Minguillon, C.; Joglar, J.; Clapés, P.
Adv. Synth. Catal. 2015, 357 (8), 1787-1807.
- Engineered L-Serine Hydroxymethyltransferase from Streptococcus thermophilus for the Synthesis of α,α-Dialkyl-α-Amino Acids.
Hernandez, K.; Zelen, I.; Petrillo, G.; Usón, I.; Wandtke, C. M.; Bujons, J.; Joglar, J.; Parella, T.; Clapés, P.
Angew. Chem. Int. Ed. 2015, 54 (10), 3013–3017.
- Expedient Synthesis of C-Aryl Carbohydrates by Consecutive Biocatalytic Benzoin and Aldol Reactions.
Hernández, K.; Parella, T.; Joglar, J.; Bujons, J.; Pohl, M.; Clapés, P.
Chem. Eur. J. 2015, 21 (8), 3335-3346.
- Disentangling Complex Mixtures of Compounds with Near-Identical 1H and 13C NMR Spectra using Pure Shift NMR Spectroscopy.
Castañar, L.; Roldán, R.; Clapés, P.; Virgili, A.; Parella, T.
Chem. Eur. J. 2015, 21 (21), 7682-7685.
- Engineering the Donor Selectivity of D-Fructose-6-Phosphate Aldolase for Biocatalytic Asymmetric Cross-Aldol Additions of Glycolaldehyde.
Szekrenyi, A.; Soler, A.; Garrabou, X.; Guerard-Helaine, C.; Parella, T.; Joglar, J.; Lemaire, M.; Bujons, J.; Clapés, P.
Chem. Eur. J. 2014, 20 (39), 12572-12583.
- Sequential Biocatalytic Aldol Reactions in Multistep Asymmetric Synthesis: Pipecolic Acid, Piperidine and Pyrrolidine (Homo)Iminocyclitol Derivatives from Achiral Building Blocks.
Soler, A.; Garrabou, X.; Hernández, K.; Gutiérrez, M. L.; Busto, E.; Bujons, J.; Parella, T.; Joglar, J.; Clapés, P.
Adv. Synth. Catal. 2014, 356 (14-15), 3007-3024.
- Aldolase-Catalyzed Synthesis of Conformationally Constrained Iminocyclitols: Preparation of Polyhydroxylated Benzopyrrolizidines and Cyclohexapyrrolizidines.
Laborda, P.; Sayago, F. J.; Cativiela, C.; Parella, T.; Joglar, J.; Clapés, P.
Org. Lett. 2014, 16 (5), 1422-1425.
- Efficient biocatalytic processes for highly valuable terminally phosphorylated C5 to C9 D-ketoses.
Guerard-Helaine, C.; Debacker, M.; Clapes, P.; Szekrenyi, A.; Helaine, V.; Lemaire, M.
Green Chem. 2014, 16 (3), 1109-1113.
- Casuarine stereoisomers from achiral substrates. Chemo-enzymatic synthesis and inhibitory properties.
Concia, A. L.; Gómez, L.; Parella, T.; Joglar, J.; Clapés, P.
- Org. Chem. 2014, 79 (11), 5386–5389.
- Chemoenzymatic synthesis, structural study and biological activity of novel indolizidine and quinolizidine iminocyclitols.
Gómez, L.; Garrabou, X.; Joglar, J.; Bujons, J.; Parella, T.; Vilaplana, C.; Cardona, P. J.; Clapés, P.
Org. Biomol. Chem. 2012, 10 (31), 6309-6321.
- Complete Switch of Reaction Specificity of an Aldolase by Directed Evolution In Vitro: Synthesis of Generic Aliphatic Aldol Products
Junker, S., Roldan, R., Joosten, H.-J., Clapés, P., Fessner, W.-D.
Angew Chem - Int Ed, 57 (32), 10153-10157(2018).
- Efficient Asymmetric Synthesis of Carbohydrates by Aldolase Nano-Confined in Lipidic Cubic Mesophases
Zhou, T., Vallooran, J.J., Assenza, S., Szekrenyi, A., Clapés, P., Mezzenga, R.
ACS Catalysis, 8 (7), 5810-5815 (2018).
- Nucleophile Promiscuity of Natural and Engineered Aldolases
Hernández, K., Szekrenyi, A., Clapés, P.
ChemBioChem, 19,1353 –1358, 2018.
- Nucleophile Promiscuity of Engineered Class II Pyruvate Aldolase YfaU from E. Coli.
Hernández, K.; Joglar, J.; Bujons, J.; Parella, T.; Clapés, P.
Angew. Chem. Int. Ed. 2018, 57 (14), 3583-3587.
- Breaking the Dogma of Aldolase Specificity: Simple Aliphatic Ketones and Aldehydes are Nucleophiles for Fructose-6-phosphate Aldolase.
Roldán, R.; Sanchez-Moreno, I.; Scheidt, T.; Hélaine, V.; Lemaire, M.; Parella, T.; Clapés, P.; Fessner, W.-D.; Guérard-Hélaine, C.
Chem. Eur. J. 2017, 23 (21), 5005-5009.
- Structure-guided redesign of D-fructose-6-phosphate aldolase from E. coli: remarkable activity and selectivity towards acceptor substrates by two-point mutation.
Gutierrez, M.; Parella, T.; Joglar, J.; Bujons, J.; Clapés, P.
Chem. Commun. 2011, 47 (20), 5762-5764.
- Redesign of the Phosphate Binding Site of L-Rhamnulose-1-Phosphate Aldolase towards a Dihydroxyacetone Dependent Aldolase.
Garrabou, X.; Joglar, J.; Parella, T.; Bujons, J.; Clapés, P.
Adv. Synth. Catal. 2011, 353 (1), 89-99.
- Asymmetric self- and cross-aldol reaction of glycolaldehyde catalyzed by D-fructose-6-phosphate aldolase.
Garrabou, X.; Castillo, J. A.; Guérard-Hélaine, C.; Parella, T.; Joglar, J.; Lemaire, M.; Clapés, P.
Angew. Chem. Int. Ed. 2009, 48, 5521-5525.
