Article
Chemistry, Multidisciplinary
Jun Zhang, Xin Li, Rongchang Chen, Xianwei Tan, Xiongduo Liu, Yaqing Ma, Fangfang Zhu, Chunyan An, Guangzheng Wei, Yongpeng Yao, Lujia Yang, Peng Zhang, Qiaqing Wu, Zhoutong Sun, Bin-Gui Wang, Shu-Shan Gao, Chengsen Cui
Summary: Imine reductases capable of accepting bulky amines have been identified using an increasing-molecule-volume-screening method, and an efficient gram-scale synthesis of an API sensipar analogue has been achieved.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Physical
Max Cardenas-Fernandez, Rebecca Roddan, Eve M. Carter, Helen C. Hailes, John M. Ward
Summary: In this study, twenty-nine novel Imine reductases (IREDs) were discovered through genome mining. These enzymes, which are NADPH-dependent, have significant biocatalytic potential for synthesizing chiral amines. The IREDs showed good activities at both pH 7 and 9 and were able to accept both NADPH and NADH as cofactors. Selected IREDs exhibited high stereoselectivity and high yields of tetrahydroisoquinolines (THIQs) when used in combination with glucose-6-phosphate dehydrogenase for NADPH cofactor recycling.
Article
Chemistry, Multidisciplinary
Jun Zhang, Daohong Liao, Rongchang Chen, Fangfang Zhu, Yaqing Ma, Lei Gao, Ge Qu, Chengsen Cui, Zhoutong Sun, Xiaoguang Lei, Shu-Shan Gao
Summary: In this study, a concise strategy combining rational design and engineering techniques was developed to enhance the substrate scope and catalytic efficiency of imine reductases (IREDs). The variant M5 exhibited superior performance and broad substrate scope for the synthesis of diverse azacycloalkylamines. This study provides exciting opportunities in medicinal and process chemistry as well as synthetic biology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Peiyuan Yao, James R. Marshall, Zefei Xu, Jesmine Lim, Simon J. Charnock, Dunming Zhu, Nicholas J. Turner
Summary: In this study, a new stereoselective biocatalytic synthesis method for N-substituted alpha-amino esters was reported, utilizing diverse metagenomic imine reductases. Both enantiomers of the target products were synthesized with high conversion and excellent enantioselectivity under mild reaction conditions. Furthermore, over 20 different preparative scale transformations were performed, demonstrating the scalability of this system.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Anshul Rajput, Tanaya Manna, Amit Mondal, Arijit De, Jhilik Mondal, Syed Masood Husain
Summary: Due to a lack of general asymmetric methodology, access to chiral substituted tetrahydro-1-, 2-, and 3-benzazepines remained limited. This study developed a general biocatalytic method using imine reductases (IREDs) for the synthesis of variously substituted chiral tetrahydro benzazepines. The reduction of seven-membered prochiral cyclic imines by selected IREDs resulted in preparative scale synthesis of chiral benzazepines with high enantiomeric excess and isolated yield.
Article
Chemistry, Physical
Itziar Penafiel, Robert A. W. Dryfe, Nicholas J. Turner, Michael F. Greaney
Summary: The integration of electro and bio-catalysis offers new ways of making molecules under very mild, environmentally benign conditions. The combined process offers a new approach to amine alkylation with native alcohols, a key bond formation in the chemical economy that is currently achieved via precious metal-catalyzed hydrogen-borrowing technologies.
Review
Chemistry, Physical
Kai Wu, Junhai Huang, Lei Shao
Summary: The synthesis of chiral amines is important in the pharmaceutical industry. IRED, a promising biocatalyst, has been found to catalyze direct asymmetric reductive amination and conjugate reduction, producing valuable amine diastereomers. This review provides insights into the catalytic mechanisms of IREDs and highlights their potential for industrial applications.
Article
Chemistry, Physical
Eric J. Ma, Elina Siirola, Charles Moore, Arkadij Kummer, Markus Stoeckli, Michael Faller, Caroline Bouquet, Fabian Eggimann, Mathieu Ligibel, Dan Huynh, Geoffrey Cutler, Luca Siegrist, Richard A. Lewis, Anne-Christine Acker, Ernst Freund, Elke Koch, Markus Vogel, Holger Schlingensiepen, Edward J. Oakeley, Radka Snajdrova
Summary: This study evaluated machine-directed evolution as an enzyme engineering strategy and found that within one cycle, it yielded a library of high-activity mutants with a significantly different activity distribution compared to traditional directed evolution. Structure-guided analysis suggested that linear additivity might provide a simple explanation for the effectiveness of machine-directed evolution in accessing chiral molecules.
Article
Chemistry, Multidisciplinary
Jade Dussart-Gautheret, Julie Yu, Krithika Ganesh, Gaikwad Rajendra, Fabrice Gallou, Bruce H. Lipshutz
Summary: This study describes the surfactant-enabled asymmetric ATA-catalyzed reductive aminations in water, which enhance the conversion levels and enable 1-pot chemoenzymatic catalysis. The modified conditions involving both biocatalysis and chemocatalysis are environmentally responsible, indicating the potential of using chemistry in water.
Article
Chemistry, Multidisciplinary
Matthias Elfinger, Timon Schoenauer, Sabrina L. J. Thomae, Robert Staeglich, Markus Drechsler, Mirijam Zobel, Juergen Senker, Rhett Kempe
Summary: The 3D metal catalyst developed here utilizes hydrogen as the reducing agent and easily handled ammonia dissolved in water as the nitrogen source for the synthesis of primary amines. The catalyst operates under mild conditions and outperforms commercially available noble metal catalysts. The key to its high activity is the unique support material it uses.
Article
Chemistry, Applied
Matthias Elfinger, Christof Bauer, Joerg Schmauch, Michael Moritz, Christoph Wichmann, Christian Papp, Rhett Kempe
Summary: This study presents an efficient method for the selective synthesis of differently substituted primary, secondary, and tertiary alkyl amines by combining borrowing hydrogen or hydrogen autotransfer and reductive amination with hydrogen. A nanostructured, bimetallic Co/Sc catalyst is used to mediate both reactions efficiently. The method shows broad product scope, good functional group tolerance, easy upscaling, and catalyst reusability.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Eve M. Carter, Esther Ambrose-Dempster, John M. Ward, Tom D. Sheppard, Helen C. Hailes
Summary: Mechanochemical reactions have emerged as a green synthetic method due to their rapidity and lower solvent usage compared to traditional approaches. This study describes the first mechanoenzymatic reactions using transaminases for amination of aldehydes and ketones, resulting in the production of amines with significantly less aqueous medium. The use of whole cells and shorter reaction times also led to high yields and stereoselectivities.
Article
Chemistry, Multidisciplinary
Arnau Rue Casamajo, Yuqi Yu, Christian Schnepel, Charlotte Morrill, Rhys Barker, Colin W. Levy, James Finnigan, Victor Spelling, Kristina Westerlund, Mark Petchey, Robert J. Sheppard, Richard J. Lewis, Francesco Falcioni, Martin A. Hayes, Nicholas J. Turner
Summary: In this study, a biocatalytic process was developed to access a specific diastereomer of a chiral amine building block used in drug discovery. The engineered biocatalyst showed high efficiency in producing the target chiral molecule and has the potential for further process development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Jia-Wang Wang, Yan Li, Wan Nie, Zhe Chang, Zi-An Yu, Yi-Fan Zhao, Xi Lu, Yao Fu
Summary: In order to increase the reliability and success rate of drug discovery, researchers have developed a new method to synthesize drug-like alpha-branched chiral amines and derivatives by nickel-catalyzed asymmetric reductive hydroalkylation of enamides and enecarbamates.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Jeremy Steflik, Amelia Gilio, Michael Burns, Gideon Grogan, Rajesh Kumar, Russell Lewis, Carlos Martinez
Summary: This study reports a method for biocatalytic reductive amination reactions, which have high potential value in pharmaceutical synthesis. The researchers identified and engineered a RedAm enzyme to catalyze the synthesis of a key intermediate for a cyclin-dependent kinase (CDK) inhibitor. The optimized enzyme variant showed high productivity at high substrate concentrations (50-fold improvement over the wild-type). Crystal structures of both the wild-type and mutant enzymes were solved to elucidate the structural changes that improved the performance of the RedAm under process conditions. This work demonstrates the versatility and industrial utility of RedAm-catalyzed reductive amination by enabling the synthesis of a chiral intermediate on a multikilogram scale.
Article
Biochemistry & Molecular Biology
Douglas Weber, David Patsch, Annika Neumann, Margit Winkler, Dorte Rother
Summary: The challenge of accessing aldehydes from carboxylate moieties was overcome by utilizing carboxylate reductases (CARs) with optimized cultivation conditions, post-translational modification, and appropriate expression strain selection to successfully increase the specific activity of Nocardia otitidiscaviarum (NoCAR) by 110-fold. This highly active NoCAR could reduce sodium benzoate to benzaldehyde with high selectivity in just 2 hours.
Article
Chemistry, Physical
Tim Gerlach, David Limanhadi Nugroho, Doerte Rother
Summary: PLP-dependent enzymes are versatile biocatalysts with various industrial applications, but they can be sensitive to light conditions in laboratory settings. One variant of amine transaminases appeared to be unaffected by light exposure and even showed increased activity within 6 hours.
Editorial Material
Chemistry, Physical
Dorte Rother, Stephan Malzacher
Article
Biochemistry & Molecular Biology
Katrin Kappauf, Nikola Majstorovic, Seema Agarwal, Dorte Rother, Christiane Claassen
Summary: Smart hydrogels, specifically poly N-acryloyl glycinamide (pNAGA) hydrogels, have been explored as a potential matrix for immobilizing enzymes, with promising results in terms of immobilization efficiency and enzyme activity. The temperature-sensitive nature of pNAGA remains intact when used to immobilize the amine transaminase, resulting in a gradual deswelling effect as temperature decreases. Although enzyme activity is primarily temperature-controlled, immobilized BmTA shows higher deactivation rates compared to free BmTA, indicating a potential deactivating effect caused by the deswelling of the pNAGA gel.
Article
Chemistry, Multidisciplinary
Moritz Doeker, Laura Grabowski, Dorte Rother, Andreas Jupke
Summary: Amine transaminase catalyzed reaction systems can efficiently produce metaraminol via extraction-based in situ product removal (ISPR), leading to higher yields and improved enzymatic production. By using l-alanine as an alternative amine donor and oleic acid as a sustainable reactant, a greener production route for metaraminol was established, overcoming thermodynamic limitations and achieving higher conversions.
Review
Chemistry, Physical
Regine Siedentop, Christiane Claassen, Doerte Rother, Stephan Luetz, Katrin Rosenthal
Summary: In vitro enzyme cascades have advantages such as strong synthetic capabilities and no need for intermediate isolation, but their performance can be influenced by various factors. Optimizing these systems is essential yet challenging.
Article
Chemistry, Applied
Jan -Dirk Sporing, William Graf von Westarp, Carina Ronja Kipp, Andreas Jupke, Dorte Rother
Summary: In this study, a simultaneous enzymatic two-step, one-pot cascade was developed for the synthesis of high purity vicinal diols. Different reaction systems for in situ product removal were compared, and purification processes for each system were developed. The results showed that in situ product removal in a biphasic reaction system significantly reduced the energy demand.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Mohamed Labib, Laura Grabowski, Christian Bruesseler, Nicolai Kallscheuer, Luisa Wachtendonk, Thomas Fuchs, Andreas Jupke, Wolfgang Wiechert, Jan Marienhagen, Doerte Rother, Stephan Noack
Summary: This study achieved the microbial production of pyruvate and L-alanine in a one-pot fermentation process, and then transformed them into Metaraminol with high yields and stereoselectivity through a series of reactions.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2022)
Article
Engineering, Chemical
Hendrik G. Mengers, Nils Guntermann, William Graf von Westarp, Andreas Jupke, Juergen Klankermayer, Lars M. Blank, Walter Leitner, Doerte Rother
Summary: This article introduces how combinations of different catalyst types can facilitate integrated reaction sequences with biogenic substrates to form bio-hybrid fuels and products.
CHEMIE INGENIEUR TECHNIK
(2022)
Article
Chemistry, Multidisciplinary
Jan-Dirk Spoering, Jan Wiesenthal, Victoria S. Pfennig, Jochem Gaetgens, Kassem Beydoun, Carsten Bolm, Juergen Klankermayer, Doerte Rother
Summary: This study demonstrates that a complete chemoenzymatic cascade to form dioxolanes can be carried out in a purely organic environment. The highly stereoselective synthesis of the product was achieved through a two-step enzyme cascade and a ruthenium molecular catalyst.
Article
Biotechnology & Applied Microbiology
Sara Jonsdottir Glaser, Sang-Hyun Pyo, Nicola Rehnberg, Dorte Rother, Rajni Hatti-Kaul
Summary: This study evaluated the use of whole cells of Escherichia coli carrying recombinant Pseudomonas fluorescens benzaldehyde lyase as biocatalysts for carboligation of 5-HMF. The results showed that using 2 g(CDW)/L recombinant cells in 10% dimethyl carbonate, pH 8.0 at 30°C yielded 81.7% DHMF and 96.7% BHMF. The DHMF concentration reached 53.0 g/L after five feeds of 20 g/L 5-HMF.
MICROBIAL CELL FACTORIES
(2023)
Article
Chemistry, Multidisciplinary
Douglas Weber, Lucas de Souza Bastos, Margit Winkler, Yeke Ni, Abil E. Aliev, Helen C. Hailes, Doerte Rother
Summary: This study presents two multi-enzyme catalysed processes to produce 1,3,4-substituted tetrahydroisoquinoline (THIQ). The reduction of 3-hydroxybenzoic acid into 3-hydroxybenzaldehyde was catalysed by a carboxylate reductase enzyme. Two different recycling approaches, using purified enzymes or lyophilised whole-cells, were established and compared, with the whole-cell system showing superior performance.
Article
Chemistry, Physical
Reinhard Oeggl, Juliane Glaser, Eric von Lieres, Dorte Rother
Summary: The implementation of biocatalysis in flow chemistry aligns with green chemistry principles, but high substrate concentrations are often hindered by solubility issues or toxicity. Continuous synthesis of (S)-2-HPP from benzaldehyde and acetaldehyde in a micro-aqueous system requires spatial distribution of acetaldehyde to maintain sub-toxic levels.
CATALYSIS SCIENCE & TECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Kevin Mack, Moritz Doeker, Laura Grabowski, Andreas Jupke, Doerte Rother
Summary: The study demonstrates the effectiveness of using the bio-based amine donor l-alanine in combination with efficient process intensification through in situ product removal for biocatalytic drug synthesis.
Review
Chemistry, Multidisciplinary
Morten M. C. H. van Schie, Jan-Dirk Sporing, Marco Bocola, Pablo Dominguez de Maria, Dorte Rother
Summary: The use of non-aqueous solvents in biocatalysis is a potential solution to increase product concentrations and decrease waste formation. Additionally, engineering protein structures can improve the efficiency of biocatalysts, while careful selection of solvent types and systems is crucial.