Synthetische Enzymkaskaden
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Wir bauen komplexe Produkte aus nachwachsenden Rohstoffen durch die Kombination von Enzymen zu synthetischen Kaskaden. Dazu kombinieren wir - modular und flexibel - Enzyme miteinander, die in der Natur nicht zusammen vorkommen. Rationales enzyme engineering, Reaktionsoptimierung und Prozessdesign werden eingesetzt, um sowohl ökonomisch als auch ökologische Effizienz zu erzielen.
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Bioeconomy Blog. Im Takt der Temperatur: das Enzym Orchester I Falling Walls Rheinland
https://blogs.fz-juelich.de/biooekonomie/2020/11/16/im-takt-der-temperatur-das-enzym-orchester/
Mit Biotech die Welt retten. Geht das? Faktencheck Folge 1
Online-Wissensmagazin zur Bio-Innovation
Konzept: Futurium Berlin | Produktion: Februar Film | Moderation: Barbara Scherle
https://www.youtube.com/playlist?list=PL1lO4YK4FC3ht0p1L77nqKF6sjdNkUk03
https://www.facebook.com/futuriumD/videos/786937728749330/
Video "MyScience". RWTH Aachen University: Prof. Dörte Rother
https://www.youtube.com/watch?v=Nil-j8a218w
DECHEMA Price 2019. Press release
https://dechema.de/Presse/Pressemitteilungen/1_2019+DECHEMA_Preis+Rother-p-20113665.html
Die Meisterin der Enzyme. Portrait in: Helmholtz Perspektiven. 01/2019: 40-42
https://www.helmholtz.de/newsroom/artikel/die-meisterin-der-enzyme/
10 Köpfe für unsere Zukunft – Nachwuchsforscher aus NRW. Bild online. 18.10.2017. http://www.bild.de/regional/ruhrgebiet/forschung/10-koepfe-fuer-unsere-zukunft-53561054.bild.html
Spöring J-D, Graf von Westarp W, Kipp C R, Jupke A, Rother D. 2022. Enzymatic Cascade in a Simultaneous, One-Pot Approach with In Situ Product Separation for the Asymmetric Production of (4S,5S)-Octanediol. Org. Process Res. Dev. DOI: 10.1021/acs.oprd.1c00433
Gerlach T, Schain J, Söltl S, van Schie M M C H, Hilgers F, Bitzenhofer N L, Drepper T, Rother D. 2022. Photo-regulation of Enzyme Activity: The Inactivation of a Carboligase with Genetically Encoded Photosensitizer Fusion Tags, Frontiers Catal. https://doi.org/10.3389/fctls.2022.835919
Doeker M, Grabowski L, Rother D, Jupke A. 2022. In situ reactive extraction with oleic acid for process intensification in amine transaminase catalyzed reactions. Green Chem. 24 (1): 295-304
Oeggl R, Glaser J, von Lieres E, Rother D. 2021. Continuous enzymatic stirred tank reactor cascade with unconventional medium yielding high concentrations of (S)-2-hydroxyphenyl propanone and its derivatives. Catal. Sci. Technol. 11: 7886 - 7897
Siedentop R, Claaßen C, Rother D, Lütz S, Rosenthal K. 2021. Getting the Most Out of Enzyme Cascades: Strategies to Optimize In Vitro Multi-Enzymatic Reactions. Catalysts. 11 (10): 1183
Kappauf K, Majstorovic N, Agarwal S, Rother D, Claaßen C. 2021. Modulation of Transaminase Activity by Encapsulation in Temperature‐Sensitive Poly (N‐acryloyl glycinamide) Hydrogels. ChemBioChem 12 (4): 1190
Gerlach T, Nugroho D L, Rother D. 2021. The effect of visible light on the catalytic activity of PLP-dependent enzymes. ChemCatChem 13: 2398-2406
Mack K, Doeker M, Grabowski L, Jupke A, Rother D. 2021. Extractive in-situ product removal for the application of naturally produced L-alanine as amine donor in enzymatic metaraminol production. Green Chem. 23: 4892-4901
Weber D, Patsch D, Neumann A, Winkler M, Rother D. 2021. Production of the carboxylate reductase from Nocardia otitidiscaviarum in a soluble, active form for in vitro applications. ChemBioChem 22, 1823
Malzacher S, Rother D. 2021. Computer-aided enzymatic retrosynthesis. News&Views article. Nature Catal. 4.2: 92-93
Van Schie M M C H., Spöring J-D, Bocola M, Domínguez de María P, Rother D. 2021. Applied biocatalysis beyond just buffers – from aqueous to unconventional media. Options and guidelines. Green Chem. 23: 3191-3206
Claaßen C, Mack K, Rother D. 2020. Benchtop NMR for online reaction monitoring of the biocatalytic synthesis of aromatic amino alcohols. ChemCatChem. 12(4): 1190-119
Contente M L, Dall’Oglio F, Annunziata F, Molinari F, Rabuffetti M, Romano D, Tamborini L, Rother D, Pinto A. 2020. Stereoselective reduction of prochiral cyclic 1,3-diketones using different biocatalysts. Catalysis Letters 150 (4): 1176-1185
Erdmann V, Sehl T, Frindi-Wosch I, Simon R C, Kroutil W, Rother D. 2019. Methoxamine Synthesis in a Biocatalytic 1-Pot 2 Step Cascade Approach. ACS Catal. 9 (8): 7380-7388
Claaßen C, Gerlach T, Rother D. 2019. Stimulus-Responsive Regulation of Enzyme Activity for One-Step and Multi-Step Syntheses. Adv. Synth. Catal. 361(11): 2387–2401
Kulig J, Sehl T, Mackfeld U, Wiechert W, Pohl M, Rother D. 2019. An Enzymatic 2-Step Cofactor and Co-Product Recycling Cascade towards a Chiral 1,2-Diol. Part I: Cascade Design. Adv. Synth. Catal. 361(11): 2607-2615
Oeggl R, Neumann T, Gätgens J, Romano D, Noack S, Rother D. 2018. Citrate as Cost-efficient NADPH regenerating agent. Front. Bioeng. Biotechnol. 6 (196)
Oeggl R, Maßmann T, Jupke A, Rother D. 2018. Four Atom Efficient Enzyme Cascades for All 4-Methoxyphenyl-1,2-propanediol Isomers Including Product Crystallization Targeting High Product Concentrations and Excellent E-Factors. ACS Sustainable Chem. Eng. 6 (9): 11819–11826
Zhang W, Fernández-Fueyo E, Ni Y, van Schie M, Gacs J, Renerie R, Wever R, Mutti F, Rother D, Alcalde M, Hollmann F. 2018. Selective aerobic oxidation reactions using a combination of photocatalytic water oxidation and enzymatic oxyfunctionalisations. Nature Catal. 1 (1): 55-62
Döbber J, Gerlach T, Offermann H, Rother D, Pohl M. 2018. Closing the gap for efficient immobilization of biocatalysts in continuous processes: HaloTag TM fusion enzymes for a continuous enzymatic cascade towards a vicinal chiral diol. Green Chem. 20: 544 - 552
Erdmann V, Lichman B R, Zhao J, Simon R C, Kroutil W, Ward J M, Hailes H C, Rother D. 2017. Enzymatic and chemoenzymatic 3-step cascades for the synthesis of stereochemically complementary trisubstituted tetrahydroisoquinolines. Angew. Chem. Int. Ed. 56 (41): 12503-12507
Maugeri Z and Rother D. 2017. Reductive Amination of Ketones Catalyzed by Whole Cell Biocatalysts Containing Imine Reductases (IREDs). J. Biotechnol. 258: 167 - 170
Schmidt S, de Almeida T P, Rother D, Hollmann F. 2017. Towards environmentally acceptable synthesis of chiral a-hydroxy ketones via oxidase-lyase cascades. Green Chem. 19 (5): 1226-1229
Sehl T, Bock S, Marx L, Maugeri Z, Walter L, Westphal R, Vogel C, Menyes U, Erhardt M, Müller M, Pohl M, Rother D. 2017. Asymmetric synthesis of (S)-phenylacetylcarbinol–closing a gap in C–C bond formation. Green Chem. 19: 380-384
Wachtmeister J, Jakoblinnert A, Rother D. 2016. Stereoselective Two-Step Biocatalysis in Organic Solvent: Toward All Stereoisomers of a 1,2-Diol at High Product Concentrations. Org. Process Res. Dev. 20 (10): 1744–1753
Buchholz P C F, Vogel C, Reusch W, Pohl M, Rother D, Spieß A, Pleiss J. 2016. BioCatNet: a database system for the integration of enzyme sequences and biocatalytic experiments. ChemBioChem 17 (21): 2093–2098
Wachtmeister J, Rother D. 2016. Recent advances in whole cell biocatalysis techniques bridging from investigative to industrial scale. Curr. Opin. Biotechnol. 42: 169–177.
Maugeri Z and Rother D. 2016. Application of imine reductases (IREDs) in micro-aqueous reaction systems. Adv. Syn. Catal. 358 (17): 2745-2750
Beigi M, Gauchenova E, Walter L, Waltzer S, Bonina F, Stillger T, Rother D, Pohl M, Müller M. 2016. Regio- and Stereoselective Aliphatic-Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis. Chem. Eur. J. 22 (39): 13000-14005
Wachtmeister J, Mennicken P, Hunold A, Rother D. 2016. Modularized Biocatalysis: Immobilization of whole cells for preparative applications in micro-aqueous organic solvents. ChemCatChem 8 (3): 607-614
García-Junceda E, Lavandera I, Rother D, Schrittwieser J H. 2015. (Chemo)enzymatic cascades – Nature’s synthetic strategy transferred to the laboratory. J. Mol. Cat. B: Enzym. 114: 1-6.
Sehl T, Maugeri Z, Rother D. 2015. Multi-step synthesis strategies towards 1,2-amino alcohols with special emphasis on phenylpropanolamines. J. Mol. Cat. B: Enzym. 114: 65-71.
Holec C, Sandkuhl D, Rother D, Kroutil W, Pietruszka J. 2015. Chemoenzymatic Synthesis towards the Active Agent Travoprost. ChemCatChem 7: 3125-3130
Westphal R, Vogel C, Schmitz C, Pleiss J, Müller M, Pohl M, Rother D. 2014. A Tailor-made Chimeric Thiamine Enzyme for the Direct Asymmetric Synthesis of (S)-Benzoins. Angew. Chem. Int. Ed. 53 (35): 9376-9379.
Ein maßgeschneidertes chimäres Thiamindiphosphat-abhängiges Enzym zur direkten asymmetrischen Synthese von (S)-Benzoinen. Angew. Chem. 126 (35): 9530-9533.
Erdmann V, Mackfeld U, Rother D, Jakoblinnert A. 2014. Enantioselective, continuous (R)- and (S)-2-butanol synthesis: achieving high space-time-yields with recombinant E. coli cells in a micro-aqueous, solvent-free reaction system. J. Biotechnol. 191: 106-112.
Jakoblinnert A, Rother D. 2014. A two-step biocatalytic cascade in micro-aqueous medium: using whole cells to obtain high concentrations of a vicinal diol. Green Chem. 16: 3472-3482.
Sehl T, Hailes H C, Ward J M, Menyes U, Pohl M, Rother D. 2014. Efficient two-step biocatalytic strategies for the synthesis of all nor(pseudo)ephedrine isomers. Green Chem. 16: 3341-3348.
Wachtmeister J, Jakoblinnert A, Kulig J, Offermann H, Rother D. 2014. Whole Cell Teabag Catalysis for the Modularisation of Synthetic Enzyme Cascades in Micro-Aqueous Systems. ChemCatChem. 6 (4): 1051-1058.
Man H, Kedziora K, Kulig J, Frank A, Lavandera-García I, Gotor-Fernández V, Rother D, Hart S, Turkenburg J P, Grogan G. 2014. Structures of alcohol dehydrogenases from Ralstonia and Sphingobium spp. reveal the molecular basis for their recognition of ‘bulky-bulky’ ketones. Top. Catal. 57:356-365.
Baraibar A G, von Lieres E, Wiechert W, Pohl M, Rother D. 2014. Effective (S)-α-hydroxy ketone production: a reaction engineering approach. Top. Catal. 57: 401-411
Sehl T, Hailes H C, Ward J M, Wardenga R, von Lieres E, Offermann H, Westphal R, Pohl M, Rother D. 2013. Two Steps in One Pot: Enzyme Cascade for the Synthesis of Nor(pseudo)ephedrine from Inexpensive Starting Materials. Angew. Chem. Int. Ed. 52 (26):6772-6775.
Zwei Schritte in einem Reaktionsgefäß: Enzymkaskaden zur selektiven Synthese von Nor(pseudo)ephedrin aus kostengünstigen Ausgangsmaterialien. Angew. Chem. 125 (26): 6904-6908.
Hailes H, Rother D, Müller M, Westphal R, Ward J M, Pleiss J, Pohl M. 2013. Engineering Stereoselectivity of ThDP-dependent Enzymes. FEBS J. 280 (24): 6374-6394.
Baraibar A G, von Lieres E, Wiechert W, Pohl M, Rother D. 2013. Effective (S)-α-hydroxy ketone production: a reaction engineering approach. Top. Catal. 57: 401-411
Westphal R, Jansen S, Vogel C, Pleiss J, Müller M, Rother D, Pohl P. 2013. MenD from Bacillus subtilis: A potent catalyst for the enantiocomplementary asymmetric synthesis of functionalized α-hydroxy ketones. ChemCatChem. 6 (4): 1082–1088.
Man H, Kedziora K, Kulig J, Frank A, Lavandera-García I, Gotor-Fernández V, Rother D, Hart S, Turkenburg J P, Grogan G. 2013. Structures of alcohol dehydrogenases from Ralstonia and Sphingobium spp. reveal the molecular basis for their recognition of ‘bulky-bulky’ ketones. Top. Catal. 57:356-365.
Westphal R, Hahn D, Mackfeld U, Waltzer S, Beigi M, Widmann M, Vogel C, Pleiss J, Müller M, Rother D, Pohl P. 2013. Tailoring (S)-selectivity of MenD from Escherichia coli. ChemCatChem. 5 (12): 3587-3594.
Westphal R, Waltzer S, Mackfeld U, Widmann M, Pleiss J, Beigi M, Müller M, Rother D, Pohl P. 2013. (S)-selective MenD variants from Escherichia coli provide access to new functionalized chiral α-hydroxy ketones. Chem. Commun. 49: 2061-2063.
Kulig J, Frese A, Kroutil W, Pohl M, Rother D. 2013. Biochemical characterization of an alcohol dehydrogenase from Ralstonia sp. Biotech. Bioeng. 110 (7): 1838-1848.
Sehl T, Simon R C, Hailes H C, Ward J M, Schell U, Pohl M, Rother D. 2012. TTC-based screening assay for ɷ-transaminases: a rapid method to detect reduction of 2-hydroxy ketones. J. Biotechnol., 159: 188-194.
Kulig J, Simon R C, Rose C A, Husain S M, Häckh M, Lüdeke S, Zeitler K, Kroutil W, Pohl M, Rother D. 2012. Stereoselective synthesis of bulky 1,2-diols with alcohol dehydrogenases. Catal. Sci. Technol., 2: 1580-1589.
Gerhards T, Mackfeld U, Bocola M, von Lieres E, Wiechert W, Pohl M, Rother D. 2012. Influence of organic solvents on enzymatic asymmetric carboligations. Adv. Synth. Catal., 354: 2805-2820.
Rother D, Kolter G, Gerhards T, Berthold CL, Gauchenova E, Knoll M, Pleiss J, Müller M, Schneider G, Pohl M. 2011. (S)-selective mixed benzoin condensation by structure-based design of the pyruvate decarboxylase from Acetobacter pasteurianus. ChemCatChem 3 (10): 1587-1596.
Khatri NK, Gocke D, Trentmann O, Neubauer P, Hoffmann F. 2011. Single-chain antibody fragment production in Pichia pastoris: Benefits of prolonged pre-induction glycerol feeding. Biotechnol. J. 6 (4): 452-462.
Gocke D, Kolter G, Müller M, Pohl M. 2010. Entwicklung einer Enzym-Plattform für die biokatalytische C-C Verknüpfung. Chem. Ing. Tech. 82: 81-86.
Gocke D, Graf T, Brosi H, Frindi-Wosch I, Walter L, Müller M, Pohl M. Comparative characterisation of thiamin diphosphate-dependent decarboxylases. 2009. J. Mol. Catal. B: Enzym. 61: 30-35.
Müller M, Gocke D, Pohl M. 2009. Thiamin diphosphate in biological chemistry: Exploitation of ThDP-dependent enzymes for asymmetric chemoenzymatic synthesis. FEBS J. 276 (11): 2894-2940.
Gocke D, Walter L, Gauchenova E, Kolter G, Knoll M, Berthold CL, Schneider G, Pleiss J, Müller M, Pohl M. 2008. Rational protein design of ThDP-dependent enzymes: engineering stereoselectivity. ChemBioChem 9: 406-412.
Gocke D, Nguyen CL, Pohl M, Stillger T, Walter L, Müller M. 2007. Branched-chain keto acid decarboxylase from Lactococcus lactis (KdcA), a valuable thiamine diphosphate-dependent enzyme for asymmetric C-C bond formation. Adv. Synth. Catal. 349: 1425-1435.
Berthold CL, Gocke D, Wood MD, Leeper FJ, Pohl M, Schneider G. 2007. Crystal structure of the branched-chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemo- and enantioselective carboligation reaction. Acta Crystallogr. Sec. D: Biol. Crystallogr. 63: 1217-1224.
Spaepen S, Versées W, Gocke D, Pohl M, Steyaert J, Vanderleyden J. 2007. Characterization of phenylpyruvate decarboxylase, involved in auxin production of Azospirillum brasilense. J. Bacteriol. 189 (21): 7626-7633.
Domínguez de María P, Pohl M, Gocke D, Gröger H, Trauthwein H, Walter L, Müller M. 2007. Asymmetric synthesis of aliphatic 2-hydroxy ketones by enzymatic carboligation of aldehydes. Eur. J. Org. Chem.: 2940-2944.
Hischer T, Gocke D, Fernandez M, Hoyos P, Alcantara AR, Sinisterra JV, Hartmeier W, Ansorge-Schumacher MB. 2005. Stereoselective synthesis of novel benzoins catalysed by benzaldehyde lyase in a gel-stabilised two-phase system. Tetrahedron 61(31): 7378-7383.
Sehl T, Kulig J, Westphal R, Rother D. 2015. Synthetic enzyme cascades for valuable diols and amino alcohols – smart composition and optimization strategies. Grunwald P, editor. Industrial Biocatalysis. Pan Stanford Publishing Pte. Ltd., Singapore, ISBN 978-981-4463-88-1 (Hardcover), 978-981-4463-89-8 (eBook)
Pohl M, Gocke D, Müller M. 2008. Thiamin-based Enzymes for Biotransformations. Anastas PT, Crabtree RH, editors. Handbook of Green Chemistry – Green Catalysis. Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA. S. 75-114.
Gocke D. 2008. New and optimised thiamine diphosphate (ThDP)-dependent enzymes for carboligation - Creation of a toolbox for chiral 2-hydroxy ketones. Institute of Molecular Enzyme Technology, Heinrich-Heine-University Düsseldorf, PhD-thesis.
Sehl T, Baraibar A G, Pohl M, Rother D. Verfahren zur Herstellung von Cathin.
PCT/EP patent 3008198, patent granted: 10.05.2017
US-patent 9,890,406, patent granted: 13.02.2018
US-patent 9,890,406, patent granted: 13.02.2018
Japanese patent 6427176, granted: 02.11.2018
Indian patent 317326, granted: 31.07.2019
Chinese patent ZL201480032090.0, granted: 26.03.2019
Sehl T, Marx L, Westphal R, Pohl M, Rother D. Lyase und für die DNA kodierende DNA, die DNA enthaltenden Vektoren sowie Verfahren zur asymmetrischen Synthese von (S)-Phenylacetylcarbinol.
US-patent 10,006,061, patent granted: 26.06.2018
PCT/EP patent 3194587, patent granted: 14.08.2019
Japanese-patent 6802167, patent granted: 30.11.2020
Chinese Patent ZL201580049907.X, patent granted: 29.10.2021
Sehl T, Marx L, Westphal R, Pohl M, Rother D. Lyase sowie Verfahren zur asymmetrischen Synthese von (S)-Phenylacetylcarbinol.
US-patent 10,465,211, patent granted: 05.11.2019
PCT/EP patent 3194588, patent granted: 21.10.2020
García Ovejero J, Marmenia I, Veintemillas Verdaguer s, Martínes de la Fuente J, Morelase Herrero M P, Grazú Bonavia M V, Guisán Sejas J M, López Gallego F, Nidetzky B, Rother D, Cassinelli N, Bernadini G B. Nanoparticles for the control of one-spot multi-enzyme eratcions.
File No priority declaration: EP21382585, patent filed: 01.07.2021