Our research in the area of Biocatalysis involves engineering of enzymes and processes for sustainable synthesis of high-value chemical products. We combine enzymology, protein engineering, in silico molecular modelling and organic chemistry to tailor enzymes for industrial conditions. An overview of our current research is given in our recent review articles.
Many thanks to previous students, postdocs and other colleagues! (list of alumni)
1. Multi-Enzyme Cascades and Reaction Engineering
There are many obstacles to overcome in order for biocatalytic reactions to be competitive. In the example of omega-transaminases, we have targeted a number of these and optimized the processes in the synthesis of chiral amines. One example is the reaction equilibrium, which needs to be displaced. This can be accomplished by removal of products or creative design of smart amino donors. We have explored this and have developed new strategies for equilibrium control. Our recent focus is to establish multi-enzyme cascade processes in one pot for high-value chemicals synthesis.
Recent selected publications from the group:
Lisa Marx, Nicolás Ríos-Lombardía, Philipp Süss, Matthias Höhne, Francisco Morís, Javier González-Sabín, Per Berglund. Chemoenzymatic Synthesis of Sertraline. Eur. J. Org. Chem. 2020, 510-513. http://dx.doi.org/10.1002/ejoc.201901810 . Published in the special issue Hot Topic: Biocatalysis
Federica Ruggieri, Luuk M. van Langen, Derek T. Logan, Björn Walse, Per Berglund. Transaminase‐catalyzed racemization with potential for dynamic kinetic resolutions. ChemCatChem 2018, 10, 5012-5018. https://doi.org/10.1002/cctc.201801049
Lisa Marx, Nicolás Ríos-Lombardía, Judith F. Farnberger, Wolfgang Kroutil, Ana I. Benítez-Mateos, Fernando López-Gallego, Francisco Morís, Javier González-Sabín* and Per Berglund*. Chemoenzymatic Approaches to the Synthesis of Cinacalcet. Adv. Synth. Catal. 2018, 360, 2157-2165. https://doi.org/10.1002/adsc.201701485. Front cover: https://doi.org/10.1002/adsc.201800499
Emese Abaházi, Péter Sátorhelyi, Balázs Erdélyi, Beáta G. Vértessy, Henrik Land, Csaba Paizs, Per Berglund and László Poppe. Covalently immobilized Trp60Cys mutant of ω-transaminase from Chromobacterium violaceumfor kinetic resolution of racemic amines in batch and continuous-flow modes. Biochem. Eng. J. 2018, 132, 270-278. https://www.sciencedirect.com/science/article/pii/S1369703X18300317?via%3Dihub
Henrik Land, Peter Hendil-Forsell, Mats Martinelle, Per Berglund. One-pot biocatalytic amine transaminase/acyl transferase cascade for aqueous formation of amides from aldehydes or ketones. Catal. Sci. Technol. 2016, 6, 2897-2900. http://dx.doi.org/10.1039/C6CY00435K
Carlos Palo-Nieto, Samson Afewerki, Mattias Anderson, Cheuk-Wai Tai, Per Berglund, Armando Córdova. Integrated Heterogeneous Metal/Enzymatic Multiple Relay Catalysis for Eco-Friendly and Asymmetric Synthesis. ACS Catal. 2016, 6, 3932-3940. http://dx.doi.org/10.1021/acscatal.6b01031
2. Enzyme Stability, Rational Design and Stereoselectivity Control
Transaminases are interesting for stereoselective synthesis of chiral amines. We have explored several S- and R-selective amine transaminases and we have determined and published the first 3D-structure of such an enzyme which is used to predict changes in the protein. Stereoselectivity is one of the most interesting properties of enzymes which make them in many cases superior to chemical alternatives. Rational ways to improve, switch and control the stereoselectivity are crucial to establish biocatalysis as a general tool. We have shown that it is possible to turn an S-selective enzyme into an R-selective one with only a single-point mutation.
Recent selected publications from the group:
Andrea Fiorati, Maria S. Humble, Per Berglund, Davide Tessaro. Employment of Transaminases in Disperse Systems for the Biotransformation of Hydrophobic Substrates. Adv. Synth. Catal. 2020, 362, 1156-1166. http://dx.doi.org/10.1002/adsc.201901434
Henrik Land, Federica Ruggieri, Anna Szekrenyi, Wolf-Dieter Fessner, Per Berglund. Engineering the Active Site of an (S)-Selective Amine Transaminase for Acceptance of Doubly Bulky Primary Amines. Adv. Synth. Catal. 2020, 362, 812-821. https://doi.org/10.1002/adsc.201901252 "VIP" (Very Important Publication) published in the special issue Hot Topic: Biocatalysis
Federica Ruggieri, Jonatan C. Campillo-Brocal, Shan Chen, Maria S. Humble, Björn Walse, Derek T. Logan, Per Berglund. Insight into the dimer dissociation process of the Chromobacterium violaceum (S)-selective amine transaminase. Sci. Rep. 2019, 9, 16946. www.nature.com/articles/s41598-019-53177-3
Henrik Land, Jonatan C. Campillo-Brocal, Maria Svedendahl Humble, Per Berglund. B‐factor Guided Proline Substitutions in Chromobacterium violaceumAmine Transaminase – An Evaluation of the Proline Rule as a Method for Enzyme Stabilization. ChemBioChem 2019, 20, 1297-1304. https://doi.org/10.1002/cbic.201800749.
Shan Chen, Jonatan C. Campillo-Brocal, Per Berglund, Maria Svedendahl Humble. Characterization of the stability of Vibrio fluvialis JS17 amine transaminase. J. Biotechnol. 2018, 282, 10-17. https://doi.org/10.1016/j.jbiotec.2018.06.309
Shan Chen, Per Berglund, Maria Svedendahl Humble. The effect of phosphate group binding cup coordination on the stability of the amine transaminase from Chromobacterium violaceum. Mol. Catal. 2018, 446, 115-123. https://www.sciencedirect.com/science/article/pii/S2468823117306818?via%3Dihub
Shan Chen, Henrik Land, Per Berglund, Maria Svedendahl Humble. Stabilization of an amine transaminase for biocatalysis. J. Mol. Catal. B: Enzym. 2016, 124, 20-28. http://dx.doi.org/10.1016/j.molcatb.2015.11.022
Fabian Steffen-Munsberg, Philipp Matzel, Miriam Sowa, Per Berglund, Uwe T. Bornscheuer, Matthias Höhne. Bacillus anthracis ω-amino acid:pyruvate transaminase employs a different mechanism for dual substrate recognition than other amine transaminases. Appl. Microbiol. Biotechnol. 2016, 100, 4511-4521. http://dx.doi.org/10.1007/s00253-015-7275-9
3. Recent Review Articles
Fei Guo, Per Berglund. Transaminase Biocatalysis: Optimization and Application. Green Chem. 2017, 19, 333-360. http://dx.doi.org/10.1039/C6GC02328B
Fabian Steffen-Munsberg, Clare Vickers, Hannes Kohls, Henrik Land, Hendrik Mallin, Alberto Nobili, Lilly Skalden, Tom van den Bergh, Henk-Jan Joosten, Per Berglund, Matthias Höhne, Uwe T. Bornscheuer. Bioinformatic analysis of a PLP-dependent enzyme superfamily suitable for biocatalytic applications. Biotechnology Advances, 2015, 33, 566–604. DOI: 10.1016/j.biotechadv.2014.12.012.
Berglund P., Humble M.S., and Branneby C. (2012) C–X Bond Formation: Transaminases as Chiral Catalysts: Mechanism, Engineering, and Applications. In: Carreira E.M. and Yamamoto H. (eds.) Comprehensive Chirality, Volume 7, pp. 390-401. Amsterdam: Elsevier. DOI: 10.1016/B978-0-08-095167-6.00723-0
Maria Svedendahl Humble, Per Berglund. Biocatalytic Promiscuity. Eur. J. Org. Chem. 2011, 2, 3391-3401. DOI: 10.1002/ejoc.201001664
Karl Hult and Per Berglund. Enzyme promiscuity: mechanism and applications. Trends Biotechnol. 2007, 25, 231-238. http://dx.doi.org/10.1016/j.tibtech.2007.03.002