BioOrganic Chemistry Research Group
Research keywords:
· biocatalysis
· asymmetric synthesis
· protein engineering
· nanocarriers
· enzyme and protein immobilization
Horizon Europe keywords:
· Advanced materials
· Health technologies, new tools and solutions
· Manufacturing technologies
· Pharmaceutical technologies
H-1111 Budapest, Szent Gellért tér 4., CH building 2nd floor 214.
+361463-3299
Introduction of the Research Group
Our research group consists of a university professor, two associate professors, two assistant professors, a university assistant professor and a departmental engineer, under whose leadership six to ten PhD students as well as dozens of university students are engaged in active research. Our research group (i) conducts research to develop known biocatalysts (e.g. hydrolase enzymes: lipases, proteases, aminoacylases) as well as novel enzymes (transaminases, ketoreductases, ammonia lyases, aminomutases and other enzymes) into robust biocatalysts. Biocatalyst developments are performed using structure-based protein modeling and enzyme engineering methods. Thus, we can improve the activity, selectivity, substrate specificity, stability and other useful properties of the enzymes involved in biotransformations in a planned way. (ii) Using new materials science and surface chemistry methods, we deal with the development of carrier families (micro- and nanostructured carriers) with fine-tunable physicochemical properties. By optimizing the processes for the attachment and separation of proteins and enzymes to the supports, we create efficient biocatalysts that can be well adapted to the desired applications. (iii) The original research with the above new biocatalysts is suitable for implementation of new chemoenzymatic processes in pharmaceutical and fine chemical, energy and bioanalytical applications, mainly using continuous flow techniques, special emphasis on development of asymmetric synthesis methods; (iv) We conduct our research in domestic and international academic collaborations, such as COST - EU, CELSA [Belgium (KU Leuven), Austria (University of Graz)], SNN [Slovenia (University of Ljubljana)], SMIS [Romania (Babes-Bolyai University)]. In addition, we are conducting an industrial cooperative PhD research program with the pharmaceutical company Hovione (Portugal) and we have received targeted research support from Gedeon Richter pharmaceutical company (Hungary) as well.
Achievements
The main results of our research group are in the fields of (i) biocatalyst, (ii) nanocarrier system and (iii) biotransformation Development, which can be used primarily for synthetic biocatalysis in the fields of pharmaceutical, fine chemicals and cosmetics industry, among others.- (i) Several new enzymes have been identified (lipase - Pseudozyma antarctica, several new bacterial and yeast phenylalanine ammonia lyases, several new archae and bacterial amine transaminases). In several cases, we improved the properties of our enzymes by structure-based genetic engineering, during which we utilized our X-ray crystallographic and protein modeling results. Enzymes are used in many forms in our research, such as whole cell systems or as pure enzymes, as well as immobilized versions thereof.
- (ii) We have achieved new results in the Development of support systems for the efficient (and in some cases selective) fixation of the above biocatalysts. We solved nanofiber fixation of lipases, PAL, transaminases, other proteins, and biomimetic metalloporphyrins; the preparation, modification of silica and nanoparticles for protein immobilization; binding onto nanotube systems (carbon, clay mineral and polymer nanotubes). In addition, bisepoxide-based protein cross-linking methods have been developed and efficient modification of macroporous support systems has been solved. We have developed patented new metal-chelation based carriers.
- (iii) With the immobilized biocatalysts (lipases, ketoreductases, ammonia lyases, transaminases, etc.) we have solved the production of several new enantiomerically pure compounds. In many instances, several of our new immobilized biocatalysts were applied in flow-through microreactors, including the Development of new magnetic nanoparticle-based reactors. Together with Gedeon Richter Pharmaceuticals, we have patented a process based on transaminase enzymes for the preparation of trans-4-aminocyclohexyl derivatives by isomerization, which may be important in the synthesis of several drug molecules.
Publications
1. Poppe, L.; Nagy, J., Hornyánszky, G.; Boros, Z. (Poppe, L.; Nógrádi, M.; Eds.): Stereochemistry and Stereoselective Synthesis – An Introduction, Weinheim-New York: Wiley-VCH Verlag KGaA, 2016.(ISBN 978-3-527-33901-3).
2. Gloge, A.; Zon, J.; Kővári, Á.; Poppe, L.; Rétey, J.: Phenylalanine Ammonia-Lyase: The Use of Its Broad Substrate Specificity for Mechanistic Investigations and Biocatalysis. Synthesis of L-Arylalanines, Chem. Eur. J., 2000, 6, 3386-3390.
(DOI: 10.1002/1521-3765(20000915)6:18<3386::AID-CHEM3386>3.0.CO;2-5)
3. Csajági, Cs.; Szatzker, G.; Tőke, E. R.; Ürge, L.; Darvas, F.; Poppe, L.: Enantiomer selective acylation of racemic alcohols by lipases in continuous-flow bioreactors, Tetrahedron:Asymmetry, 2008, 19, 237-246.
(DOI: 10.1016/j.tetasy.2008.01.002)
4. Weiser, D.; Nagy, F.; Bánóczi, G.; Oláh, M.; Farkas, A.; Szilágyi, A.; László, K.; Gellért, Á.; Marosi, G.; Kemény, S.; Poppe, L.: Immobilization engineering – How to design advanced sol-gel systems for biocatalysis? Green Chem. 2017, 19(16), 3927-3937.
(DOI: 10.1039/C7GC00896A)
5. Bata, Z.; Molnár, Z.; Madaras-Koncz, E.; Molnár, B.; Sánta-Bell, E.; Varga, A.; Leveles, I.; Qian, R.; Hammerschmidt, F.; Paizs, C.; Vértessy, B. G.; Poppe, L.: Substrate Tunnel Engineering Aided by X-Ray Crystallography and Functional Dynamics Swaps the Function of MIO-Enzymes. ACS Catalysis. 2021, 11, 4538–4549.
(DOI: 10.1021/acscatal.1c00266)
Patents
1. a) Dianóczki, Cs .; Kővári, J .; Novák, L .; Poppe, L .; Recseg, K. (Bunge Ltd, Hungary): Process for the production of conjugated linoleic acid. Hung. Pat., HU 227137 B1 (2010) b) Dianóczki, Cs .; Kővári, J .; Novak, L .; Poppe, L .; Recseg, K. (Bunge Növényolajipari Rt, Hung.): METHOD FOR THE PREPARATION OF CONJUGATED LINOLEIC ACID Eur. Pat., EP 1709144 B1 (2010) 2. Sevella, B .; Kupcsulik, B .; Németh, Á .; Novák, L; Poppe, L .; Dukai, J .; Nagy, F .: Process for the preparation of 1,3-propanediol by biotransformation. Hung. Pat., HU 227235 B1 (2011) 3. a) Poppe, L .; Boros, Z .; Vértessy, B .; Kovács, K .; Tóth, A .; Hornyánszky. G .; Nagy, J .; Transylvania, B .; Bódai, V .; Sátorhelyi, P. (BME-Fermentia Kft): Carriers complexed with lanthanide metal ions suitable for binding and separation of proteins. Hung. Pat., HU 230585 B1 (2016). b) Poppe, L .; Boros, Z .; Vértessy, B .; Kovács, K .; Tóth, A .; Hornyánszky. G .; Nagy, J .; Transylvania, B .; Bódai, V .; Sátorhelyi, P. (BME-Fermentia Kft): Compositions for binding and separating of proteins. Eur Pat. EP2943501 (B1) June 26, 2019. 4. Hornyánszky. G .; Poppe, L .; Farkas, E .; Incze, D. J .; Sharp, J .; Sánta-Bell, E .; Molnár, Z. K. (Richter Gedeon Nyrt-BME): Process to produce (1r, 4r)-4-substituted cyclohexane-1-amines, Hung. Pat. Appl., P2100325, 15/09/2021.Awards
Not relevantJournals
Prestigious journals from leading scientific publishers (> 50% in D1 and Q1 journals): ACS (ASC Catalysis, ACS Sust. Chem. Eng., Organic Letters,…); RSC (Green Chem., Org. Biomol. Chem., RSC Adv.,…), Wiley (ChemSusChem, ChemCatChem, ChemBioChem, Adv. Synth. Catal., Chem. Eur. J.,…), Elsevier (Cat. Today , Tetrahedron, Proc. Biochem.,…), Springer-Nature (Sci. Rep.,…). Presentations and posters of leading international conference series (BioCat, BioTrans, IMTB, Novel Enzymes,…).Infrastructure
(i) Biocatalyst identification and modification facilities: our molecular biology laboratory enables heterologous bacterial expression and purification of different proteins. A high-pressure homogenizer is available to disrupt the cells. In addition to the production of the proteins used by the group, we also carry out enzyme engineering developments. (ii) Our group uses conventional laboratory equipment and high-pressure autoclaves to produce nanoparticles and electrospinning devices to form nanofiber systems. With our ZetaSizer we can perform nanoparticle size / charge tests, with our optical microscope we can aid the analysis of the microfibers / particles. In addition to standard synthetic laboratory equipment, we have several high-capacity thermostatic shakers to perform support enhancements and bioreactions. (iii) Biocatalytic reactions with substrates obtained by conventional synthetic organic chemistry methods can be performed by biotransformations using thermostated batch reactors (shakers) and/or various flow-through reactors. For the analysis of the products, we have GC (3 devices), HPLC (4 devices) with normal and chiral stationary phases, as well as FT-IR, UV-Vis, Raman spectrophotometers / detectors / plate-reader. (iv) Our close cooperation with national and international research groups further expands our research opportunities. National: Prof. Beáta G. Vértessy (BME Department of Applied Biotechnology and Food Science, and Institute of Enzymology, Eötvös Loránd RN); Dr. András Szilágyi and Prof. Krisztina László (BME Department of Physical Chemistry and Materials Science), Dr. Attila Bóta (RCNS Eötvös Loránd RN). International: Prof. C. Paizs (Babes-Bólyai University, Cluj-Napoca, Romania), Prof. Igor Plazl and Prof. Plona Znidarzic-Plazl (University of Ljubljana, Slovenia), Prof. Wolfgang Kroutil (University of Graz, Austria).Projects
International project- Systems Biocatalysis (SysBiocat), Action CM1303, (2013-2017), EU COST (Poppe László - Hungarian Member of Committee (MC, 2013-2017) and leader of WG5 “Process Intensification” (WG5 2013-2017))
- Enzyme Immobilization and Microfluidics for Systems Biocatalysis - NEMSyB POC-2015 P-37-273, (2016-2020), EU funding, in Romania: (László Poppe, research project director (part-time), Babes-Bolyai University, Cluj-Napoca, Romania)
National research project
- Automation of protein purification for rapid testing of known resins / supports and development of new affinity chromatography supports, KMR_12-1-2012-0140, (2013-2015), NDA (project leader: László Poppe)
- MIO-enzyme-based multistep syntheses in continuous-flow microfluidic reactor systems, SNN-125637, (2018-2020), OTKA - NKFIH (project leader: Poppe László)
National industrial project
- Investigation of the availability of industrial manufacturability criteria in the production of the TACE intermediate of Cariprazine (Richter Theme Application 21), (2021-2023), Richter Gedeon Zrt (project leader: Gábor Hornyánszky)
Industry relations
- Hungarian small and medium-sized enterprises: Dr. Balázs Erdélyi (Fermentia Kft, former joint KMR project); Dr. Csaba Csajági (Luminochem Kft., Former joint KMR project), Dr. Zsófia Bata (Dr. BATA Zrt., Running Cooperative Doctoral Program project)- Hungarian pharmaceutical companies: Richter Gedeon Zrt (joint patent, running Cooperative Doctoral Program project, running Richter topic competition), TEVA Zrt (smaller KKs, expertise), Servier (EGIS: smaller KKs, expertise), Sanofi (EUROAPI: expertise)
- Foreign company: Hovione Pharmaceuticals (Portugal: Joint Research PhD project)
Conferences
- BioTrans 2017, Budapest, July 3-7, 2017, principal organizer: László Poppe, a significant part of the professional organizing work was done by young researchers of BioOrganic Chemistry RG- BioTrans Steering Committee: permanent member, 2017-, László Poppe
- IMTB 2022, Portoroz, Slovenia, 5-7 June 2021, Plenary Speaker, László Poppe