Review
Biotechnology & Applied Microbiology
Mi Liu, Dan Wei, Zexing Wen, Jian-bo Wang
Summary: The creation of C-C bonds is an effective strategy for constructing complex compounds, and biocatalysts show higher selectivities compared to chemical catalysts, making them excellent candidates for stereoselective C-C bond formation. Progress has been made in the past decade in stereoselective C-C bond formation using aldolases and hydroxynitrile lyases, which will enable the development of new routes for the stereoselective construction of C-C bonds.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Inorganic & Nuclear
Ke Wang, Heng Li, Lin Yang, Zhen-Jiang Liu, Zi-Jian Yao
Summary: Half-sandwich ruthenium complexes based on arylhydrazoneligands were synthesized and showed high catalytic activity in the synthesis of cyanosilylethers. A new class of N,O-coordinate half-sandwich ruthenium complexes supported by hydrazone ligands were obtained with moderate to excellent yields. These air- and moisture-stable ruthenium complexes exhibited excellent catalytic activity in cyanosilylethers synthesis under mild reaction conditions.
INORGANIC CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Shuke Wu, Radka Snajdrova, Jeffrey C. Moore, Kai Baldenius, Uwe T. Bornscheuer
Summary: Biocatalysis is widely used as an alternative to chemical catalysis in various fields, with enzymes playing a key role in organic synthesis, particularly in the production of chiral compounds for pharmaceuticals and flavors. Biocatalysts are also utilized on a large scale for the production of specialty and bulk chemicals. This review focuses on scalable chemical production using enzymes, discussing opportunities, limitations, and emerging enzyme classes through illustrative examples.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Organic
Badipatla Vishnu Priya, Santosh Kumar Padhi
Summary: Hydroxynitrile lyases (HNLs) are enzymes of significant importance in organic synthesis, primarily catalyzing the stereoselective synthesis of cyanohydrins, and also carrying out asymmetric nitroaldol synthesis. Recent discoveries and developments in HNLs have expanded their synthetic scope and enhanced their catalytic ability through engineering. HNLs show promise in biocatalytic applications, including the synthesis of chiral alpha-cyanohydrins and beta-nitroalcohols, substrate selectivity, and enantioselectivity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Johannes Gottschalk, Miriam Assmann, Juergen Kuballa, Lothar Elling
Summary: The study focused on enzymatic synthesis of industrial hyaluronic acid, using immobilized cascade enzymes on magnetic beads to increase productivity and facilitate enzyme recovery. Results showed successful production of high-quality HA in repetitive batches.
Article
Agricultural Engineering
Derek Troiano, Valerie Orsat, Marie-Josee Dumont
Summary: This study explores the use of filamentous fungi as oxidative biocatalysts, focusing on the oxidation of HMF. Among the five fungal species tested, A. niger and T. reesei showed superior performance and potential for conversion into FDCA through a chemo-biocatalytic reaction system. The optimized one-pot chemo-biocatalytic cascade system achieved an 88% molar yield of FDCA after 80 hours.
BIORESOURCE TECHNOLOGY
(2022)
Review
Chemistry, Physical
Lucy C. Ward, Hannah V. McCue, Andrew J. Carnell
Summary: The review focuses on the potential use of carboxyl methyltransferases (CMTs) in industrial biotechnology, highlighting their ability to generate diverse methyl esters under aqueous conditions. Strategies for regenerating the required cofactor S-adenosylmethionine (SAM) are discussed, which will further improve the industrial applications of CMTs.
Article
Biotechnology & Applied Microbiology
Bo Pilgaard, Marlene Vuillemin, Line Munk, Jesper Holck, Sebastian Meier, Casper Wilkens, Anne S. Meyer
Summary: This study reports the discovery of a set of six complementary glucuronan lyase enzymes in the mycoparasite Trichoderma parareseei. The major finding of this study is that the majority of these lyases are induced when T. parareesei is inoculated on Basidiomycete cell walls that contain glucuronan. The study also reveals putative glucuronan lyase encoding genes in a wealth of other fungi, suggesting that fungal cell wall glucuronan is a target C-source for many types of fungi. The findings may have important implications for controlled production of glucuronan oligomers for advanced pharmaceutical applications and the development of new fungal biocontrol agents.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yangbin Shen, Luqi Wang, Ziwen Xu, Fandi Ning, Yulu Zhan, Chuang Bai, Xiaochun Zhou
Summary: This study successfully developed a novel reaction pathway for low-temperature methanol reforming through synergistic catalysis, improving hydrogen production efficiency and showing potential for commercial applications.
Article
Chemistry, Multidisciplinary
Douglas J. Fansher, David R. J. Palmer
Summary: In this article, a biocatalytic nitro-Michael addition reaction catalyzed by NahE was reported. The reaction proceeds at room temperature with low catalyst loading, providing moderate to excellent enantioselectivity and high yields. A variety of β-nitrostyrenes reacted with pyruvate in the presence of NahE, giving β-aryl-γ-nitrobutyric acids in up to 99% yield after oxidative decarboxylation. This reaction represents the first example of an aldolase displaying promiscuous Michaelase activity and enables the use of nitroalkenes as substrates for aldolases.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Elif Erdem, Lenny Malihan-Yap, Leen Assil-Companioni, Hanna Grimm, Giovanni Davide Barone, Carole Serveau-Avesque, Agnes Amouric, Katia Duquesne, Veronique de Berardinis, Yagut Allahverdiyeva, Veronique Alphand, Robert Kourist
Summary: BVMOXeno is a highly efficient Baeyer-Villiger monooxygenase with higher reaction rates and lower KM value compared to currently known BVMOs, almost completely suppressing unwanted side reactions. The recombinant production of BVMO in cyanobacteria allows more efficient utilization of water and oxygen generated by photosynthesis.
Article
Chemistry, Multidisciplinary
Chao Shou, Yu-Cong Zheng, Jing-Ru Zhan, Chun-Xiu Li, Jian-He Xu
Summary: A new method has been developed for microbial synthesis of plant-based (-)-menthol, with significantly increased production by replacing inefficient enzymes from Mentha piperita. This lays a reliable foundation for the microbial synthesis of (-)-menthol.
Article
Chemistry, Multidisciplinary
Katerina Brodsky, Kristyna Kanova, Dorota Konvalinkova, Kristyna Slamova, Helena Pelantova, Katerina Valentova, Pavla Bojarova, Vladimir Kren, Lucie Petraskova
Summary: Enzymatic sulfation is an important and understudied topic, and finding suitable sulfate donors is a major challenge. This study investigated the impact of different sulfate donors on enzyme-catalyzed sulfation, and evaluated the sulfated compounds obtained.
Article
Biochemistry & Molecular Biology
Pal Csuka, Zsofia Molnar, Veronika Toth, Ali Obaid Imarah, Diana Balogh-Weiser, Beata G. Vertessy, Laszlo Poppe
Summary: In this study, the AAL coding gene from Pseudomonas fluorescens R124 was identified and successfully expressed in E. coli. The purified PfAAL showed high activity and the immobilization on MNP nanoparticles improved its storage stability and recyclability.
Article
Biochemistry & Molecular Biology
Sariah Giraldo-Narcizo, Nihal Guenani, Ana Maria Sanchez-Perez, Antonio Guerrero
Summary: Polyethylene terephthalate (PET) is widely used for single-use applications and using enzymes to hydrolyze PET for sustainable recycling is a promising method. However, the accessibility of the enzyme to the hydrolysable chemical bonds is a challenge. In this study, alkali pre-treatment was used to modify the surface of the plastic and increase the degradation yield.
Article
Multidisciplinary Sciences
Vedat Durmaz, Katharina Koechl, Andreas Krassnigg, Lena Parigger, Michael Hetmann, Amit Singh, Daniel Nutz, Alexander Korsunsky, Ursula Kahler, Centina Koenig, Lee Chang, Marius Krebs, Riccardo Bassetto, Tea Pavkov-Keller, Verena Resch, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: This study used bioinformatics analysis to investigate the impact of SARS-CoV-2 variants on the affinity to the human receptor hACE2, with the latest Omicron variant showing the largest impact on the RBD binding interface compared to other variants. Omicron exhibited a higher ACE2 binding affinity than the wild type and requires special attention and monitoring.
SCIENTIFIC REPORTS
(2022)
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
Multidisciplinary Sciences
Katharina Koechl, Tobias Schopper, Vedat Durmaz, Lena Parigger, Amit Singh, Andreas Krassnigg, Marco Cespugli, Wei Wu, Xiaoli Yang, Yanchong Zhang, Welson Wen-Shang Wang, Crystal Selluski, Tiehan Zhao, Xin Zhang, Caihong Bai, Leon Lin, Yuxiang Hu, Zhiwei Xie, Zaihui Zhang, Jun Yan, Kurt Zatloukal, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: Treatment of COVID-19 using soluble ACE2 shows promise, but it requires optimization for emerging viral variants. This study utilized molecular dynamics simulations and a convolutional neural network to assess the binding affinity of multiple spike RBD/hACE2 variants. The high-affinity candidates hACE2-Fc K31W and multi-mutation variants were validated in vitro and their binding affinities with Omicron BA.3, Omicron BA.4/BA.5, and Omicron BA.2.75 RBDs were evaluated in silico. The candidates produced in Nicotiana benthamiana showed significantly reduced IC50 compared to those produced in CHO cells and wild-type hACE2-Fc.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Applied
Sergio Gonzalez-Granda, Georg Steinkellner, Karl Gruber, Ivan Lavandera, Vicente Gotor-Fernandez
Summary: The combination of gold(I) and enzyme catalysis allows for the selective synthesis of a series of nor(pseudo)ephedrine derivatives. This approach involves the hydration of 1-phenylprop-2-yn-1-yl acetate or N-(1-phenylprop-2-yn-1-yl)acetamide using IPrAuNTf2 catalyst, followed by (dynamic) asymmetric biotransamination or bioreduction of the resulting keto ester or keto amide intermediates. Enzyme actions exhibit high stereoselectivity towards methyl ketones, enabling the synthesis of enantio- and diastereomerically enriched products. The use of propargyl esters or amides as starting materials allows for the production of amino alcohol, diol, and diamine derivatives with good yields and high (stereo)selectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Engineering, Chemical
Birgit Grill, Tea Pavkov-Keller, Christoph Grininger, Barbara Darnhofer, Karl Gruber, Melanie Hall, Helmut Schwab, Kerstin Steiner
Summary: Oxidative alkene cleavage is a promising method for synthesizing aldehydes and ketones. The Mn-dependent protein TM1459 from Thermotoga maritima can undergo alkene cleavage of styrene derivatives in the presence of tert-butyl hydroperoxide. However, the enzyme is prone to inactivation due to auto-oxidation in the oxidative environment required for the cleavage reaction. By replacing oxidizable residues, the stability of TM1459 was improved, leading to increased enzyme activity. However, the residue exchanges also affected metal binding.
CHEMIE INGENIEUR TECHNIK
(2023)
Article
Chemistry, Physical
Andrea M. Chanique, Nakia Polidori, Lucija Sovic, Daniel Kracher, Leen Assil-Companioni, Philipp Galuska, Loreto P. Parra, Karl Gruber, Robert Kourist
Summary: Cold-active enzymes have optimal activity at low temperatures, making them useful for preserving heat-sensitive compounds. A cold-active flavin-dependent monooxygenase (FMO) was discovered in an Antarctic organism, showing high activity between 5 and 25 degrees C and promiscuity towards NADH and NADPH. The enzyme exhibits high enantioselectivity and has a unique active site structure.
News Item
Biotechnology & Applied Microbiology
Karl Gruber, Lisa Melton
Summary: A new generation of companies is exploring the use of insect larvae as a protein source for various purposes, including animal feed, fertilizer, biofuels, and food ingredients. Insects offer a cheaper and more sustainable alternative to traditional soy and fishmeal, and can be raised on organic waste.
NATURE BIOTECHNOLOGY
(2023)
Article
Microbiology
Lena Parigger, Andreas Krassnigg, Stefan Grabuschnig, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: The monkeypox virus, similar to smallpox, has caused a recent outbreak affecting 110 countries. Understanding the virus at a molecular level is crucial for studying infection processes, predicting changes, and guiding drug and vaccine development. A study of the virus's structural proteome identified 10,580 candidate open reading frames, which were narrowed down to 1,079 suspected proteins, including 210 representative proteins. These findings provide valuable information for drug discovery, mutational analysis, and vaccine development. Atomistic 3D models of the proteins, including drug-binding sites, were also generated.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Physical
Andrea M. Chanique, Nakia Polidori, Lucija Sovic, Daniel Kracher, Leen Assil-Companioni, Philipp Galuska, Loreto P. Parra, Karl Gruber, Robert Kourist
Summary: Cold-active enzymes maintain high activity at low temperatures, making them useful for avoiding side reactions and preserving heat sensitive compounds. Through genome mining, a cold-active enzyme was discovered in an Antarctic organism, showing high activity at temperatures between 5 and 25 degrees C and displaying promiscuity towards NADH and NADPH, as well as a wide range of ketones and thioesters.
Meeting Abstract
Biochemistry & Molecular Biology
Amit Amit, Nakia Polidori, Karl Gruber
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
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
Medicine, General & Internal
Lena Parigger, Andreas Krassnigg, Tobias Schopper, Amit Singh, Katharina Tappler, Katharina Koechl, Michael Hetmann, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: This study analyzed genomic data of SARS-CoV-2 main protease (M-pro), revealing an accelerated mutational dynamics since December 2021, particularly in a region near the active site. The increased mutational variability in this area may suggest the onset of antiviral resistance development, highlighting the importance of further monitoring and consideration in ongoing drug development.
FRONTIERS IN MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Julia Pitzer, Kerstin Steiner, Christian Schmid, Viktor K. Schein, Christoph Prause, Claudia Kniely, Michaela Reif, Martina Geier, Elena Pietrich, Tamara Reiter, Philipp Selig, Clemens Stuckler, Peter Pochlauer, Georg Steinkellner, Karl Gruber, Helmut Schwab, Anton Glieder, Wolfgang Kroutil
Summary: This study describes an enzyme-catalyzed, racemization-free amidation reaction in an organic solvent for the synthesis of l-prolinamide. Through comprehensive reaction, solvent, and enzyme engineering, high concentrations of the desired product were obtained with excellent optical purity (>99%). This innovative industrial process provides a key intermediate for drug synthesis while avoiding racemization, halogenated solvents, and waste, significantly improving atom efficiency.
