Review
Biochemical Research Methods
Jieran Yi, Zhi Li
Summary: Artificial multi-enzyme cascades have the potential to synthesize useful natural molecules from natural substrates and simple chemicals. Strategies such as protein engineering and cofactor regeneration can improve the efficiency of these cascades.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Article
Chemistry, Physical
William Finnigan, Lorna J. Hepworth, Sabine L. Flitsch, Nicholas J. Turner
Summary: With the expanding enzyme toolbox for biocatalysis, there is potential for constructing powerful enzymatic cascades for efficient and selective synthesis of target molecules. RetroBioCat is an intuitive tool for computer-aided design of biocatalytic cascades, utilizing expertly encoded reaction rules and literature precedent to identify promising biocatalytic pathways.
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
Chemistry, Multidisciplinary
Rui Yang, Zeyu Zhou, Huanfeng Jiang, Toh-Seok Kam, Kai Chen, Zhiqiang Ma
Summary: The first asymmetric total synthesis of the monoterpenoid indole alkaloid arboduridine has been achieved. The synthesis involves several reactions to construct the complex structure and demonstrates a highly enantioselective synthetic strategy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Minghui Zhu, Qinglong Zhang, Weiwei Zi
Summary: The study presents a dual-metal catalyzed diastereodivergent coupling method for the synthesis of beta-amino alcohols with multiple stereoisomers, enabling the concise preparation of natural products such as mycestericins F and G.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Zhikun Zhang, Xile Hu
Summary: A catalytic deracemization method for secondary benzylic alcohols has been developed, utilizing sequential photochemical dehydrogenation followed by enantioselective thermal hydrogenation. The combination of a heterogeneous dehydrogenation photocatalyst and a chiral molecular hydrogenation catalyst enables the conversion of racemic aryl alkyl alcohols into their enantiomerically enriched forms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Eleanor M. Landwehr, Meghan A. Baker, Takuya Oguma, Hannah E. Burdge, Takahiro Kawajiri, Ryan A. Shenvi
Summary: Neuroactive metabolites from the bark of Galbulimima belgraveana exhibit varying distributions among trees and are challenging to access through chemical synthesis due to intricate bond networks and dense stereochemistry. However, a new synthetic approach has been developed to reduce the synthetic burden and increase efficiency, allowing for further chemical exploration and biological investigation in Galbulimima alkaloid space.
Article
Chemistry, Physical
Zhitong Zhao, Chengyi Wang, Qipeng Chen, Yu Wang, Rui Xiao, Chunxia Tan, Guohua Liu
Summary: By developing a supported dual catalysts system, the conflicts between oxidative and reductive catalysts were overcome, resulting in an efficient one-pot redox deracemization of secondary alcohols. This process demonstrated enhanced yields and enantioselectivities compared to unsupported dual catalysts systems.
Article
Chemistry, Multidisciplinary
Yiyin Liu, Liangyan Zhu, Xuemei Li, Yunfeng Cui, Atefeh Roosta, Jinhui Feng, Xi Chen, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: In this study, a redox-neutral photocatalysis/enzymatic catalysis system was developed for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C-C coupling. This strategy not only enables the efficient synthesis of a series of chiral amino alcohols in a green and sustainable manner but also has potential for the synthesis of bioactive molecules through novel C-C radical coupling transformations.
Review
Chemistry, Multidisciplinary
Yubo Jiang, Ryan E. McNamee, Philip J. Smith, Ana Sozanschi, Zixuan Tong, Edward A. Anderson
Summary: Cascade reactions, also known as domino reactions, are a powerful means to construct multiple ring systems in a single step. This review discusses highlights in cascade polycyclizations applied to natural product syntheses over the last five years, including various processes such as pericyclic, ionic, metal-catalyzed, organocatalytic, and radical processes. Emphasis is placed on significant advancements in each field, such as photochemical and electrochemical methods, novel biomimetic routes, and enantioselective cascades.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Physical
Yan Zhang, F. Wieland Goetzke, Kirsten E. Christensen, Stephen P. Fletcher
Summary: In this study, we report an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds. By using a Rh-catalyzed reaction, a racemic N-Boc-nortropane-derived allylic chloride was coupled with (hetero)aryl boronic esters via an asymmetric Suzuki-Miyaura-type cross-coupling reaction, and an unexpected kinetic resolution was achieved. The enantiopure allyl chloride obtained can undergo highly enantiospecific reactions. This method was applied in the formal synthesis of YZJ-1139(1) with high stereoselectivity.
Review
Chemistry, Organic
Christian Ascaso-Alegre, Juan Mangas-Sanchez
Summary: Inspired by nature, synthetic chemists are trying to mimic the efficient metabolic networks in living organisms to build complex molecules by combining different types of catalysts in the same reaction vessel. This highly multidisciplinary field benefits from advances in chemical catalysis, molecular biology and reaction engineering, and is rapidly progressing towards higher productivity and lower waste generation and cost in synthetic procedures.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
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)
Review
Chemistry, Physical
Shengyuan Guo, Tristan Asset, Plamen Atanassov
Summary: The translation discusses the importance of reducing carbon dioxide emissions and transforming them into value-added chemicals through the development of electrochemical catalytic processes. Different classes of electrocatalysts, enzymatic catalysts, and bacterial cells are integrated for the cascade reactions, forming complex hydrocarbons and organic molecules for industrial applications. The interconnected pathways of electrocatalysts and cascade reactions are summarized in a descriptive map highlighting critical reaction routes.
Article
Biochemistry & Molecular Biology
Hannes Frohnmeyer, Lothar Elling
Summary: Nucleotide sugars are essential for the synthesis of glycans, polysaccharides, and glyco-conjugates in various industries. However, the high costs and limited availability of nucleotide sugars hinder their large-scale industrial applications. Therefore, research focus has shifted towards nucleotide sugar synthesis strategies to overcome these limitations.
CARBOHYDRATE RESEARCH
(2023)
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, 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
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.
Article
Chemistry, Physical
Ashleigh J. Burke, Thomas M. Lister, James R. Marshall, Murray J. B. Brown, Richard Lloyd, Anthony P. Green, Nicholas J. Turner
Summary: Reductive aminases (RedAms) have shown potential in catalyzing coupling reactions between primary amines and aldehydes/ketones, leading to the synthesis of chiral secondary amines. However, the synthesis of tertiary amines, especially from coupling ketones with secondary amines, has been challenging. In this study, we demonstrated that RedAms, specifically RedAm-361 engineered through directed evolution, can selectively catalyze reductive aminations of cyclic secondary amines with carbonyl partners, including dynamic kinetic resolutions and enantioselective aminations. These biotransformations provide access to important structural motifs found in active pharmaceutical ingredients and other bioactive molecules. The discovery and engineering of RedAms have significant implications for the development of industrial biocatalysts in the production of key pharmaceutical intermediates.
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, 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, Physical
Amelia K. Gilio, Thomas W. Thorpe, Alex Heyam, Mark R. Petchey, Balazs Pogranyi, Scott P. France, Roger M. Howard, Michael J. Karmilowicz, Russell Lewis, Nicholas Turner, Gideon Grogan
Summary: Imine reductases (IREDs) catalyze the reduction of cyclic imines and the coupling of ketones and amines, forming secondary amine products. IR77 enzyme was found to catalyze the coupling of larger bicyclic amines with cyclohexanone. Mutant IR77-A208N with improved activity for amine product formation was successfully synthesized using structure-guided mutagenesis.
Article
Chemistry, Multidisciplinary
Jack J. Sangster, Rebecca E. Ruscoe, Sebastian C. Cosgrove, Juan Mangas-Sanchez, Nicholas J. Turner
Summary: Here, we present a one-pot, chemoenzymatic process for synthesizing enantioenriched C(1)-allylated tetrahydroisoquinolines. This process involves the oxidation of monoamine oxidase (MAO-N) catalyst and the allylboration of a metal catalyst, followed by a biocatalytic deracemization, resulting in high yields and good to high enantiomeric excess of allylic amine derivatives. This cascade reaction is simple to operate, with all components added at the beginning of the reaction, and can produce key building blocks for further elaboration.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(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
Amelia K. Gilio, Thomas W. Thorpe, Alex Heyam, Mark R. Petchey, Balazs Pogranyi, Scott P. France, Roger M. Howard, Michael J. Karmilowicz, Russell Lewis, Nicholas Turner, Gideon Grogan
Summary: Imine reductases (IREDs) can catalyze the reduction of cyclic imines and the coupling of ketones and amines to form secondary amine products. Previous studies mainly focused on using small hydrophobic amines, but for certain pharmaceutical targets, larger amines are required. In this study, the enzyme IR77 from Ensifer adhaerens was found to be a promising biocatalyst for the reductive amination of cyclohexanone with pyrrolidine. The mutant IR77-A208N showed improved activity for amine product formation, leading to isolated yields of up to 93% for the amination of cyclohexanone with larger amines.
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.
Review
Chemistry, Multidisciplinary
Bo Yuan, Dameng Yang, Ge Qu, Nicholas J. Turner, Zhoutong Sun
Summary: This review summarizes the advancements in NAD(P)H-dependent amine dehydrogenases and imine reductases as biocatalysts for asymmetric reductive amination to produce optically active amines. These enzymes exhibit high activity and stereoselectivity, and can utilize a wide range of substrates. By discussing the evolutionary history, substrate scope, and applications of these enzymes, the review provides an outlook on emerging industrial biotechnologies for chiral amine production.
CHEMICAL SOCIETY REVIEWS
(2023)
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.
