BIOTRANSFORMACIÓ I MOLÈCULES BIOACTIVES
Responsable científic: Pere Clapés
La recerca del nostre grup es centra en el desenvolupament i optimització de biocatalitzadors nous i existents per a la formació de vincles carboni-carboni (carbolligases). Les carbolligases tenen el potencial d’accedir de forma eficient als bastides moleculars complexos a partir de materials de partida senzills, amb estereoselectivitat sense precedents i sense necessitat de passos iteratius tediosos i que requereixen temps per a la protecció i desprotecció de grups funcionals sensibles o reactius.
Es persegueixen tres objectius:
- desenvolupar un nou procés eficient en termes econòmics i respectuosos amb el medi ambient per a la indústria de la fabricació de productes químics
- produir nous compostos (és a dir, nous tipus d’estructura que generen diversitat molecular) accessible per a les investigacions en el descobriment de fàrmacs i
- l’enginyeria del biocatalitzador millorant la seva tolerància al substrat, estereoselectivitat i propietats catalítiques (és a dir, cap a reaccions no naturals) per ampliar la seva finestra d’aplicabilitat. La investigació inclou models computacionals per a la interacció de lligands-proteïnes essencials per a l’optimització de biocatalitzadors mitjançant l’enginyeria de proteïnes guiada per l’estructura.
Web personal: https://pereclapes.wordpress.com/
- Carbolligases com a biocatalizadors en la formació asimètrica d’enllaços carboni-carboni. Les carboligases són components fonamentals de la metodologia quimioenzimàtica. La nostra investigació inclou el cribratge, la producció mitjançant un procés fermentatiu de ceps recombinants sobreexpressats, la seva valoració com a biocatalizador en les reaccions orgàniques objectiu i el seu redisseny per alterar l’activitat i la selectivitat.
- Carbolligases i xenocarboligases artificials construïdes per modificació química de proteïnes amb cofactors artificials o per enginyeria de proteïnes mitjançant la introducció d’aminoàcids no codificats convenientment funcionalitzats (ncAA) que contenen amines secundàries i terciàries utilitzant el mètode de supressió del codó de aturada (SCS).
- Els models computacionals per a les interaccions de lligands-proteïnes per ajudar a redissenyar o modificar racionalment els biocatalizadors i les molècules biològicament actives d’interès són de gran importància.
- Les molècules sintetitzades utilitzant carbolligases inclouen: iminosugars, carbohidrats, desoxisúcars, derivats, cetoàcids, aminoàcids i anàlegs
Paraules clau: biocatàlisis, enginyeria de proteïnes, síntesi orgànica, síntesi quimioenzimàtica, aldolases: dihidroxiacetona (DHA) que utilitzen aldolases, aldolases dependents de fosfat de la dihidroxiacetona (DHAP), aldolases de glicina i enzims relacionats, piruvat aldolases i enzims relacionats.
Personal científic
Pere Clapés
Professor Investigació
pere.clapes@iqac.csic.es
Jesús Joglar
Científic Titular
jesus.joglar@iqac.csic.es
Jordi Bujons
Científic Titular
jordi.bujons@iqac.csic.es
Personal de laboratori
Karel Hernández
Investigador postdoctoral
karel.hernandez@iqac.csic.es
Carlos José Moreno
Investigador predoctoral
carlos.moreno@iqac.csic.es
Saurabh Ahirwar
Investigador predoctoral
saurabh.ahirwar@iqac.csic.es
- Degradation of organophosphate flame retardants by white-rot fungi: Degradation pathways and associated toxicity
Losantos, Diana, Fernández-Arribas, Julio, Pérez-Trujillo, Míriam, Eljarrat, Ethel, Sarrà, Montserrat, Caminal, Glòria,
Science of the Total Environment, 959,178260, 2025 - Removal of TBP sorbed on wood by Trametes versicolor through solid-state fermentation
Diana Losantos, Montserrat Sarra, Glòria Caminal
Journal of Hazardous Materials, Volume 480, 5 December 2024, 136066 - OPFR removal by white rot fungi: screening of removers and approach to the removal mechanism
Losantos, D., Sarra, M., Caminal, G.
Frontiers in Fungal Biology, 5, art. no. 1387541, 2024.
- A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane
Font-Mateu, J., Sanllehí, P., Sot, J., Abad, B., Mateos, N., Torreno-Pina, J.A., Ferrari, R., Wright, R.H.G., Garcia-Parajo, M.F., Joglar, J., Goñi, F.M., Beato, M.
Cellular and Molecular Life Sciences, 81 (1), art. no. 98, 2024
- Novel method for rapid monitoring of OPFRs by LLE and GC–MS as a tool for assessing biodegradation: validation and applicability
Losantos, D., Palacios, O., Berge, M.J., Sarrà, M., Caminal, G., Eustaquio, A.
Analytical and Bioanalytical Chemistry, 416 (6), pp. 1493-1504, 2024
- Expanding Synthetic Applications of Δ1-Piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate Reductase from Pseudomonas syringae (DpkAPsyrin). Biocatalytic Asymmetric Synthesis of (S,E)-2-hydroxy-4-arylbut-3-enoic Acid Derivatives
Moreno, C.J., Gittings, S., Schollmeyer, D., Joglar, J., Bujons, J., Hernández, K., Clapés, P.
Advanced Synthesis and Catalysis, 366 (4), pp. 990-1000. 2024
- Biocatalytic Transamination of Aldolase-Derived 3-Hydroxy Ketones
Pickl, M., Ebner, M., Gittings, S., Clapés, P., Kroutil, W.
Advanced Synthesis and Catalysis, 365 (9), pp. 1485-1495. 2023
- Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
Moreno, C.J., Hernández, K., Gittings, S., Bolte, M., Joglar, J., Bujons, J., Parella, T., Clapés, P.
ACS Catalysis, 13 (8), pp. 5348-5357. 2023
- Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney
Méndez, L., Muñoz, S., Barros, L., Miralles-Pérez, B., Romeu, M., Ramos-Romero, S., Torres, J.L., Medina, I.
Antioxidants, 12 (3), art. no. 751, 2023.
- 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.
