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.
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
Qi Jin, Jingqi Zhang, Shuangping Huang, Lili Gao, Honghong Chang, Jiandong Zhang
Summary: A novel fully biocatalytic system was developed for the direct stereoselective hydroamination of aryl alkenes to produce chiral amines. The process involves sequential alkene asymmetric hydration catalyzed by hydratase (HD), followed by in situ oxidation of alcohol into ketone by two enantiocomplementary alcohol dehydrogenases (ADHs), and finally, enantioselective transformation of ketone into enantiomerically pure amine by γ-transaminase (TA). This research achievement provides a highly selective, highly atom-economical, green and sustainable method for synthesizing chiral amines from alkenes via formal alkene asymmetric hydroamination.
Article
Chemistry, Physical
Fulong Li, Yan Du, Youxiang Liang, Yuwen Wei, Yukun Zheng, Huimin Yu
Summary: This study redesigned a trans-aminase enzyme to enhance its catalytic efficiency towards bulky N-heterocyclic compounds. A variant with significant activity enhancement was obtained by fine-tuning the substrate-binding pocket with a simplified amino acid alphabet. The most active variant exhibited 1064-fold greater catalytic efficiency and improved activity towards a series of cyclic and bulky heterocyclic ketones. It also showed successful gram-scale synthesis of a chiral N-heterocyclic amine.
Article
Chemistry, Applied
Mathias Pickl, Markus Ebner, Samantha Gittings, Pere Clapes, Wolfgang Kroutil
Summary: Although optical pure amino alcohols are highly demanded, their synthesis remains challenging due to the requirement of elaborate protection strategies. This study presents a multi-enzymatic methodology that allows the synthesis of enantioenriched 1,3-amino alcohols from commodity chemicals. By utilizing a Type I aldolase and enzymatic transamination, both diastereomers of the 1,3-amino alcohol motif were accessible, resulting in the desired amino alcohols with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Wei Zhao, Wenji Wang, Huan Zhou, Qishan Liu, Zhiqing Ma, Haizhou Huang, Mingxin Chang
Summary: A one-pot asymmetric hydrogenation of pyridines with subsequent N-alkylation using a traceless Bronsted acid activation strategy is reported. The reaction exhibits high stereoselectivity and can be used to synthesize indolizidines and quinolizidines. Experimental and theoretical studies reveal that chloride anion and noncovalent interactions play important roles in determining the stereoselectivity of the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hua-Hua Wang, Hui Shao, Guanglong Huang, Jianqiang Fan, Wai-Pong To, Li Dang, Yungen Liu, Chi-Ming Che
Summary: In this study, chiral iron porphyrin complexes were found to catalyze the asymmetric intramolecular C(sp(3))-H amination of aryl and arylsulfonyl azides, providing chiral indolines and benzofused cyclic sulfonamides, respectively. The reactions exhibited high enantioselectivity (up to 93% ee) and high yields (up to 99%) under mild conditions with 410 nm light.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Peng Zhang, Xiao-Mei Wang, Qi Xu, Chang-Qiu Guo, Peng Wang, Chuan-Jun Lu, Ren-Rong Liu
Summary: In this study, a Pd-catalyzed cross-coupling strategy was employed for the synthesis of N-C axially chiral biaryl molecules with excellent enantioselectivities and good yields. The practicality of this reaction was demonstrated in the synthesis of biologically relevant molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Donglei Wang, Ying-Bo Shao, Yunrong Chen, Xiao-Song Xue, Xiaoyu Yang
Summary: An efficient method for the asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been developed using chiral phosphoric acid catalysis for enantioselective electrophilic aromatic aminations with azodicarboxylates. This method allows for the synthesis of a wide range of chiral macrocycles with varying ring sizes and functional groups, achieving high yields and enantioselectivities. The mechanism and origins of the stereoselectivities of these reactions were investigated through experimental studies and computational calculations. Preliminary utilization of the planar-chiral macrocycle as a chiral organocatalyst demonstrated the potential applications of these novel chiral skeletons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Madan R. Gopal, Roman M. Dickey, Neil D. Butler, Michael R. Talley, Daniel T. Nakamura, Ashlesha Mohapatra, Mary P. Watson, Wilfred Chen, Aditya M. Kunjapur
Summary: In order to incentivize the collection of plastic wastes, chemical transformations that add value to plastic deconstruction products need to be developed. This study demonstrates the production of useful building blocks from PET deconstruction products through the design of one-pot biocatalytic transformations. By coupling the highest activity reductase with an omega-transaminase, valuable plastic building blocks can be produced efficiently.
Article
Biotechnology & Applied Microbiology
Hui-Jue Zhu, Jiang Pan, Chun-Xiu Li, Fei-Fei Chen, Jian-He Xu
Summary: This study reports a novel biocatalytic route for synthesizing (+)-Neomenthylamine using ω-transaminase. By screening, an ω-transaminase from Vibrio fluvialis JS17 was found to have significant amination activity to (-)-menthone, and under optimized conditions, 10 mM (-)-menthone was transformed into 4.7 mM product in 24 hours. This biocatalytic route using inexpensive starting materials and mild reaction conditions provides an easy and green approach for the synthesis of (+)-Neomenthylamine and highlights the potential of biocatalysts in the synthesis of unnatural terpenoid amine derivatives.
BIORESOURCES AND BIOPROCESSING
(2023)
Article
Chemistry, Multidisciplinary
Ruke Wang, Xuan Tang, Xinchun Jv, Yaxu Liu, Bo Wang
Summary: In this study, a novel palladium-based nanocatalyst is introduced, which selectively catalyzes the reductive amination of carbonyl compounds, enabling the in situ regeneration of amino donors from wasteful co-products in a one-enzyme cascade using ?-transaminase, without the requirement of the expensive coenzyme NAD(P)H. The cascade combines ?-transaminase-assisted transamination with a selective reductive amination reaction facilitated by a heterogeneous palladium-based nanocatalyst, achieving exceptional yields of chiral amines up to 99% and excellent enantioselectivity. This chemoenzymatic one-enzyme transamination-reductive amination cascade network is highly atom-efficient and generates H2O as its sole by-product, demonstrating its potential impact in synthetic chemistry and beyond.
Article
Chemistry, Multidisciplinary
Markus Hobisch, Jelena Spasic, Lenny Malihan-Yap, Giovanni Davide Barone, Kathrin Castiglione, Paula Tamagnini, Selin Kara, Robert Kourist
Summary: This study demonstrates the use of internal illumination to overcome the cell density limitation of cyanobacterial biotransformations, achieving high reaction rates in a scalable photobioreactor.
Article
Chemistry, Multidisciplinary
Suchen Zou, Bangkui Yu, Hanmin Huang
Summary: An efficient strategy for preventing beta-hydride elimination of alkylpalladium species by ligating palladium with adjacent amino group was developed, enabling a novel palladium-catalyzed ring-closing aminoalkylative amination of unactivated aminoenynes. The reaction is applicable to aminals and aliphatic aldehydes with secondary amines, providing straightforward access to structurally diverse exocyclic allenic amines with 5 to 12-membered N-heterocycles. A chiral phosphoramidite-ligated palladium complex was used as the catalyst to achieve an enantioselective variant with up to 93% ee. Synthetic transformations of the chiral products also resulted in structurally unique spirodiamines, including one pharmaceutically active molecule, through axial-to-central chirality transfer.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Soumyadeep Chakrabortty, Shasha Zheng, Fabian Kallmeier, Eszter Barath, Sergey Tin, Johannes G. de Vries
Summary: A readily available chiral Ru/bisphosphine catalyst was used to achieve the direct asymmetric reductive amination of bio-based levulinic acid (LA) to produce enantioenriched 5-methylpyrrolidinone with excellent enantioselectivity (up to 96% ee) and high isolated yield (up to 89%). Methyl levulinate (ML), a byproduct from the industrial production of 2,5-furandicarboxylic acid (FDCA), can be used as a substitute for LA with similar reactivity and selectivity. Mass spectrometry and isotope labelling studies suggest that the chiral lactam is formed through imine-enamine tautomerization/cyclization followed by asymmetric hydrogenation of the cyclic enamide.
Review
Biochemistry & Molecular Biology
Grazia Malovan, Bettina Hierzberger, Samuele Suraci, Maximilian Schaefer, Karine Santos, Shalinee Jha, Peter Macheroux
Summary: This review focuses on recent advances in understanding the structure, catalytic activity, and physiological relevance of Dipeptidyl peptidase 3 (DPP3). The article highlights the broader role of DPP3 as a valuable biomarker in cardiovascular and renal pathologies, as well as its potential as a promising drug target.
Editorial Material
Biochemistry & Molecular Biology
Eleni Skourti, Peter Macheroux
Summary: Peter Macheroux is a Professor of Biochemistry and Head of the Institute of Biochemistry at Graz University of Technology in Austria. His research has made significant contributions to bacterial enzymology, plant physiology, and our understanding of human disease pathways. His team has identified DPP3 as a biomarker for cardiovascular diseases and explored its therapeutic implications. In this interview, Peter provides an overview of his research focus and goals, highlights some of his scientific breakthroughs, and discusses the current challenges in his field.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Guleck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime moiety to amine group has recently been discovered, but the reaction pathway remained unclear. Through studying crystal structures, molecular dynamics simulations, and investigating biocatalytic cascades and intermediates, evidence suggests that the reaction proceeds via an imine intermediate rather than a hydroxylamine intermediate. The imine is further reduced by the ene-reductase to produce the amine product. A non-canonical tyrosine residue contributes to the catalytic activity by protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Applied
Philipp Petermeier, Christoph Kohlfuerst, Ana Torvisco, Roland C. C. Fischer, Alejandro Mata, Doris Dallinger, C. Oliver Kappe, Joerg H. H. Schrittwieser, Wolfgang Kroutil
Summary: Substituted piperidine rings are efficiently prepared with multiple stereocentres using multi-enzymatic and chemo-enzymatic methods from achiral diketoester precursors. Highly enantioselective transamination and diastereoselective reduction processes enable the synthesis of optically pure piperidines. This approach offers a more streamlined and efficient route for the synthesis of trisubstituted piperidines with potential applications in drug discovery.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
P. Petermeier, C. Kohlfuerst, A. Torvisco, R. C. Fischer, A. Mata, D. Dallinger, C. O. Kappe, J. H. Schrittwieser, W. Kroutil
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
Mathias Pickl, Markus Ebner, Samantha Gittings, Pere Clapes, Wolfgang Kroutil
Summary: Although optical pure amino alcohols are highly demanded, their synthesis remains challenging due to the requirement of elaborate protection strategies. This study presents a multi-enzymatic methodology that allows the synthesis of enantioenriched 1,3-amino alcohols from commodity chemicals. By utilizing a Type I aldolase and enzymatic transamination, both diastereomers of the 1,3-amino alcohol motif were accessible, resulting in the desired amino alcohols with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Sarah A. Berger, Christopher Grimm, Jonathan Nyenhuis, Stefan E. Payer, Isabel Oroz-Guinea, Joerg H. Schrittwieser, Wolfgang Kroutil
Summary: Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography. However, their limited use is due to the requirement of specialised and expensive hardware. We demonstrate that a common platform, single-quadrupole HPLC-MS, can be used for rapid analysis of diverse biotransformations by flow-injection mass spectrometry (FIA-MS), providing validated activity and selectivity information with a one-minute analytical run time per sample. Our results establish FIA-MS as a versatile and reliable alternative to traditional methods for screening enzymatic reactions.
Review
Chemistry, Physical
Veronique Alphand, Willem J. H. van Berkel, Valentina Jurkas, Selin Kara, Robert Kourist, Wolfgang Kroutil, Francesco Mascia, Marc M. Nowaczyk, Caroline E. Paul, Sandy Schmidt, Jelena Spasic, Paula Tamagnini, Christoph K. Winkler
Summary: The recent increase of interest in photocatalysis has expanded to biocatalysis and led to a surge in the development of light-dependent enzyme-mediated or enzyme-coupled processes. Reviewing the progress in photobiocatalysis, we suggest categorizing it into different disciplines and providing guidelines for reporting research results and performing photobiocatalytic reactions. Overall, we believe that this field enhances the diversity of biocatalytic reactions and harnesses the selectivity of enzymes in photocatalysis. We anticipate that the ongoing enthusiasm for light-dependent enzymatic processes will uncover new photobiocatalytic mechanisms, complementing biocatalysis with novel bond-forming reactions and innovative strategies for utilizing light as a sustainable energy source.
Article
Chemistry, Organic
Beata Zdun, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: We developed chemoenzymatic routes using low-cost starting materials and enzyme preparations to synthesize tenofovir. The key step involved stereoselective reduction or kinetic resolution using alcohol dehydrogenase or lipase as biocatalysts. By employing immobilized lipase in a mixture of vinyl acetate and toluene, the desired (R)-ester was obtained with high yield and optical purity. Alternatively, reduction of a ketone using lyophilized E. coli cells containing recombinant alcohol dehydrogenase resulted in excellent conversion and yield of the corresponding (R)-alcohol. The enzymatic strategy could be applied in the synthesis of tenofovir prodrug derivatives.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Correction
Chemistry, Physical
Stefan Simic, Migle Jakstaite, Wilhelm T. S. Huck, Christoph K. Winkler, Wolfgang Kroutil
Article
Chemistry, Multidisciplinary
Aleksandra Rudzka, Beata Zdun, Natalia Antos, Lia Martinez Montero, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: There is a need for biocatalysts capable of transferring hydrogen to prepare optically pure alcohols, especially for sterically demanding ketones. This study describes the biocatalytic potential of an anti-Prelog (R)-specific variant of Lactobacillus kefir ADH as a whole-cell biocatalyst for the reduction of prochiral carbonyl substrates. The results show that the biocatalyst exhibits activity towards a variety of ketones, producing optically active alcohol products with high conversion and excellent stereoselectivity.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Christopher Grimm, Simona Pompei, Kristina Egger, Michael Fuchs, Wolfgang Kroutil
Summary: Lignin-derived aryl methyl ethers have potential as carbon sources in chemistry. An alternative method for their demethylation is through cobalamin-dependent enzymes, which require a methyltransferase and a carrier protein. Fusion proteins, connecting the methyltransferase with the corrinoid-binding protein, showed better performance than separate proteins, enabling a simpler protocol for demethylation. The fusion enzyme has promising applications in diversifying natural products and valorizing lignin.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Glueck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime to amine has been observed in ene-reductases transforming alpha-oximo beta-keto esters. Through structural analysis, molecular dynamics simulations, biocatalytic cascades, and investigation of possible intermediates, it has been determined that the reaction proceeds via an imine intermediate and not through a hydroxylamine intermediate. A non-canonical tyrosine residue in ene-reductase OPR3 was found to play a role in protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Multidisciplinary
Emmanuel Cigan, Jakob Pletz, Sarah A. Berger, Bettina Hierzberger, Michael Grilec-Zlamal, Alexander Steiner, Isabel Oroz-Guinea, Wolfgang Kroutil
Summary: This study demonstrates an efficient access to the morphinan scaffold using a combination of organic synthesis and enzymatic reactions. The synthesis of a medicinally important compound class, promorphinans, was achieved by minimizing protecting group techniques and utilizing biocatalysis.
Article
Chemistry, Physical
Pawel Borowiecki, Aleksandra Rudzka, Tamara Reiter, Wolfgang Kroutil
Summary: In this study, a sequential chemoenzymatic one-pot two-step deracemization protocol was developed for synthesizing enantiomeric Lisofylline. The protocol involved a tandem bi-enzymatic oxidation-reduction reaction sequence, which catalyzed the oxidation of Lisofylline to pentoxifylline using laccase and a redox mediator, and the subsequent reduction of pentoxifylline to generate enantiomeric Lisofylline using alcohol dehydrogenases. The method showcased high conversion rates and synthesis efficiency, providing both antipodes of Lisofylline in good yields and high enantiomeric excess.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)
