Article
Chemistry, Multidisciplinary
Christina Felbek, Steffen Hardt, Cecilia Papini, Debajyoti Pramanik, Vincent Artero, Marc Fontecave, Vincent Fourmond, Nicolas Plumere, Christophe Leger
Summary: Through experiments under conditions of mediated electron transfer, we have demonstrated that the dinuclear active site of [FeFe] hydrogenase can be inserted into the apo-enzyme embedded in a film of redox polymer, with maturation monitored by electrochemistry at a rate comparable to direct electron transfer. This new approach paves the way for the implementation of hydrogenases in large scale real-life processes.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Francisco J. Arriaza-Gallardo, Sebastian Schaupp, Yu-Cong Zheng, Mohd Farid Abdul-Halim, Hui-Jie Pan, Joerg Kahnt, Georgia Angelidou, Nicole Paczia, Xile Hu, Kyle Costa, Seigo Shima
Summary: This study reveals the functions of two enzymes, HcgA and HcgG, in the biosynthesis of the FeGP cofactor through in vitro complementation experiments and the use of purified enzymes. The results show that HcgA catalyzes the formation of 1, and HcgG is responsible for the reactions after the biosynthesis of 3. The data suggest that HcgG contributes to the formation of CO and completes the biosynthesis of the FeGP cofactor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biotechnology & Applied Microbiology
Jochem R. Nielsen, Ruud A. Weusthuis, Wei E. Huang
Summary: Enzymes in commercial bioproduction require high efficiency, robustness, and specificity. Enzyme engineering techniques like random mutagenesis and directed evolution are often used to achieve these properties. Growth-coupling selection strategies can be used to select enzyme variants based on improved cofactor oxidation or reduction rates. This review summarizes the metabolic engineering involved in creating strains auxotrophic for the oxidized or reduced state of redox cofactors and highlights the successful applications of this technique in enzyme engineering.
BIOTECHNOLOGY ADVANCES
(2023)
Review
Microbiology
Rhys Grinter, Chris Greening
Summary: F-420, a redox cofactor produced by many bacteria and archaea, has unique catalytic properties, playing important roles in various redox reactions. Significant progress has been made in understanding its distribution, biosynthesis, function, and applications in recent years.
FEMS MICROBIOLOGY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Sebastian Schaupp, Francisco J. Arriaza-Gallardo, Hui-jie Pan, Joerg Kahnt, Georgia Angelidou, Nicole Paczia, Kyle Costa, Xile Hu, Seigo Shima
Summary: In this study, an in vitro biosynthesis assay of the FeGP cofactor was conducted using cell extract of a specific bacterium, revealing that pyridinol derivatives 1, 2, and 3 are precursors of the FeGP cofactor, with the carboxy group of 3 being converted to the acyl ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Adrien Pagnier, Batuhan Balci, Eric M. Shepard, William E. Broderick, Joan B. Broderick
Summary: The assembly and installation of the [FeFe]-hydrogenase H-cluster is not fully understood, but in vitro approaches using semisynthetic and enzyme-based methods have provided new insights into the maturation process. These approaches have shed light on the roles of individual maturation enzymes, the nature of H-cluster assembly intermediates, the molecular precursors of H-cluster ligands, and the sequence of steps involved in [FeFe]-hydrogenase maturation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Microbiology
Pier Francesco Di Leonardo, Giacomo Antonicelli, Valeria Agostino, Angela Re
Summary: Understanding the organizational and functional properties of hydrogen metabolism is crucial for creating a framework to support a hydrogen-fueled low-carbon economy. This study investigated the genomes of several industrially relevant acetogens and identified their hydrogenases' repertoire. The findings provide valuable knowledge on the functional specificity and potential applications of hydrogenases in biotechnological processes.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Faisal Hayat, Manoj Sonavane, Mikhail V. Makarov, Samuel A. J. Trammell, Pamela McPherson, Natalie R. Gassman, Marie E. Migaud
Summary: This study provides a comprehensive characterization of pyridones and their formation, identifying a ribosylated form of one of the pyridones that causes cell death. The research demonstrates that this form of pyridone leads to autophagy-related cell death at physiological levels found in the plasma of AKI patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Multidisciplinary
Victor K. Sharma, Justin M. Hutchison, Alan M. Allgeier
Summary: Enzymatic processes capable of redox reactions are of increasing research interest, with a focus on the regeneration of expensive cofactors required by the enzymes. Alternative methods such as chemical, electrochemical, and photochemical regeneration offer enhanced efficiency and operational simplicity compared to enzymatic regeneration. This comprehensive Review discusses various methods of NAD(P)H cofactor regeneration, quantitatively compares their performance, and identifies barriers and future opportunities for improving the efficiency and sustainability of oxidoreductase processes.
Review
Chemistry, Multidisciplinary
Chao Wang, Zhenli Lai, Gangfeng Huang, Hui-Jie Pan
Summary: This review summarizes the major progresses on [Fe]-hydrogenase, including its structural characterisation, catalytic mechanism, cofactor biosynthesis, mimetic model development, and artificial enzymes construction. The challenges and opportunities of this enzyme and its mimetic systems in the application of synthetic chemistry and others are also discussed.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Inorganic & Nuclear
Konstantin Laun, Iuliia Baranova, Jifu Duan, Leonie Kertess, Florian Wittkamp, Ulf-Peter Apfel, Thomas Happe, Moritz Senger, Sven T. Stripp
Summary: [FeFe]-hydrogenases are excellent H-2 evolution catalysts with active site cofactor comprising a [4Fe-4S] cluster linked to a diiron site with carbon monoxide and cyanide ligands. Proton transfer pathways and pH differences affect the stabilization of electrons at different cofactor states, influencing the hydrogen turnover process.
DALTON TRANSACTIONS
(2021)
Article
Multidisciplinary Sciences
Harsha Gouda, Romila Mascarenhas, Markus Ruetz, Madeline Yaw, Ruma Banerjee
Summary: This study identifies an unconventional strategy for controlling metal redox state by using bivalent molecular mimicry with ADP to protect against cob(II)alamin overoxidation. ADP induces a conformational change that seals off solvent access, exerting control over the metal oxidation state. This research reveals the importance of metabolites in preserving and recycling a rare, essential metal cofactor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Rieke Haas, Vera Engelbrecht, Oliver Lampret, Shanika Yadav, Ulf-Peter Apfel, Silke Leimkuehler, Thomas Happe
Summary: The active site of [FeFe]-hydrogenases contains a cubane [4Fe4S]-cluster and a unique diiron cluster with biologically unusual CO and CN ligands. The biogenesis of the diiron site, termed [2FeH], requires the involvement of maturation proteins HydE, HydF, and HydG. However, our study suggests that the proposed binding mechanism and the presence of a [4Fe-4S]-cluster in HydF are not involved in the binding or transfer of [2Fe(P)].
Article
Chemistry, Multidisciplinary
Oren Ben-Zvi, Itzhak Grinberg, Asuka A. Orr, Dror Noy, Phanourios Tamamis, Iftach Yacoby, Lihi Adler-Abramovich
Summary: The study demonstrates that a specific dipeptide hydrogelator can encapsulate oxygen, restrict its diffusion and penetration in the hydrogel. The mechanism involves pockets formed between aromatic rings in the supramolecular structure to bind oxygen, maintaining the activity of oxygen-sensitive enzymes.
Editorial Material
Chemistry, Multidisciplinary
Mrinalini G. Walawalkar, Priya Pandey, Ramaswamy Murugavel
Summary: The recent discoveries of dicationic and monoanionic ferrocene derivatives shed light on the impact of substituents on the C-5 ring and the selection of redox agents and solvent systems in preparing previously thought difficult synthetic targets. These oxidized and reduced forms of ferrocene are of interest to spectroscopists, magnetochemists, and theoreticians.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Patricia Rodriguez-Macia, Leonie Kertess, Jan Burnik, James A. Birrell, Eckhard Hofmann, Wolfgang Lubitz, Thomas Happe, Olaf Ruediger
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Physical
Vera Engelbrecht, Kristina Liedtke, Andreas Rutz, Shanika Yadav, Alexander Guenzel, Thomas Happe
Summary: Understanding the algal hydrogen metabolism is crucial for the biotechnological exploitation of photosynthetic H-2 production. The two [FeFe]-hydrogenases in Chlamydomonas reinhardtii, HYDA1 and HYDA2, exhibit differences in their affinity to oxidised PETF and catalytic preference for consuming H-2, suggesting potential roles and mechanisms that require further investigation.
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
(2021)
Article
Chemistry, Physical
Clare F. Megarity, Bhavin Siritanaratkul, Ryan A. Herold, Giorgio Morello, Fraser A. Armstrong
JOURNAL OF CHEMICAL PHYSICS
(2020)
Article
Multidisciplinary Sciences
Giorgio Morello, Clare F. Megarity, Fraser A. Armstrong
Summary: Multistep enzyme-catalyzed cascade reactions within nanocompartments are highly efficient by electrochemically recycling cofactors, leading to high reaction rates and minimized intermediate loss. This approach shows promise for studying and exploiting complex biocatalytic pathways.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Martin Winkler, Jifu Duan, Andreas Rutz, Christina Felbek, Lisa Scholtysek, Oliver Lampret, Jan Jaenecke, Ulf-Peter Apfel, Gianfranco Gilardi, Francesca Valetti, Vincent Fourmond, Eckhard Hofmann, Christophe Leger, Thomas Happe
Summary: The protein morphing mechanism of [FeFe]-hydrogenase CbA5H controls the reversible transition between catalytic and inactive states, with a conserved cysteine residue protecting the active site from oxygen by acting as a safety cap. This protection mechanism is regulated by three non-conserved amino acids located approximately 13 angstrom away from the active site, demonstrating remote control of the first coordination sphere chemistry of the H-cluster.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Lei Wan, Rachel S. Heath, Clare F. Megarity, Adam J. Sills, Ryan A. Herold, Nicholas J. Turner, Fraser A. Armstrong
Summary: The ability to drive and observe rapid enzyme catalysis in both directions is achieved by immobilizing cascade components within electrode nanopores and coupling reactions to fast, quasi-reversible NADP(+)/ NADPH electrochemistry. By using two electrodes in sequence, each containing an enantioselective alcohol dehydrogenase for one halfcycle, efficient one-pot de-racemizers can be achieved.
Article
Chemistry, Physical
Ryan A. Herold, Raphael Reinbold, Clare F. Megarity, Martine Abboud, Christopher J. Schofield, Fraser A. Armstrong
Summary: This study demonstrates how human isocitrate dehydrogenase (IDH1) and its cancer-associated variant (IDH1 R132H) can be rendered electroactive by coconfining with a NADP(H) recycling enzyme in nanopores formed within an electrode. This enables real-time monitoring of IDH activity and redox landscape, mimicking the accumulation of the oncometabolite 2-hydroxyglutarate in the presence of the R132H variant. The technique also allows for time-resolved measurements of drug binding and dissociation kinetics.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Clare F. Megarity, Thomas R. I. Weald, Rachel S. Heath, Nicholas J. Turner, Fraser A. Armstrong
Summary: The importance of energized nanoconfinement in facilitating the study and execution of enzyme cascades with multiple exchangeable cofactors is demonstrated through experiments with carboxylic acid reductase.
Review
Chemistry, Multidisciplinary
Fraser A. Armstrong, Beichen Cheng, Ryan A. Herold, Clare F. Megarity, Bhavin Siritanaratkul
Summary: Protein film electrochemistry (PFE) provides valuable insights into the properties and behaviors of redox proteins and electron-transferring enzymes, allowing the study of previously unclear aspects such as unstable Fe-S centers and enzyme catalytic biases. By attaching enzymes to electrodes, their reversible electrocatalytic capabilities have been revealed, and interesting similarities between catalytic rates and electronics have been observed. One particular case involves the reversible electrochemistry of a photosynthetic enzyme, ferredoxin-NADP+ reductase (FNR), which has led to the development of a new technology called cascade-tronics, where reactions in enzyme cascades can be monitored and controlled using an electrochemical analyzer. The electrochemical leaf (e-Leaf) offers a natural way to study enzyme behaviors under nanoconfinement and crowding, mimicking the conditions in living cells.
Article
Chemistry, Multidisciplinary
Beichen Cheng, Rachel S. Heath, Nicholas J. Turner, Fraser A. Armstrong, Clare F. Megarity
Summary: This study successfully achieved deracemisation and stereoinversion of secondary alcohols using a single electrode in one pot by exploiting the unique ability of the 'electrochemical leaf' system to drive and control nanoconfined enzyme cascades bidirectionally while directly monitoring their rate as electrical current in real-time. The method offers high yield and ease of operation.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Melanie Heghmanns, Andreas Rutz, Yury Kutin, Vera Engelbrecht, Martin Winkler, Thomas Happe, Muege Kasanmascheff
Summary: In this study, the active center of CbA5H, the H-cluster, was characterized using multifrequency continuous wave and pulsed electron paramagnetic resonance spectroscopy. It was found that under oxidizing conditions, an additional radical species dominates the spectra. The generation of this radical signal depends on the presence of an intact H-cluster and a complete proton transfer pathway.
Article
Chemistry, Inorganic & Nuclear
Konstantin Laun, Iuliia Baranova, Jifu Duan, Leonie Kertess, Florian Wittkamp, Ulf-Peter Apfel, Thomas Happe, Moritz Senger, Sven T. Stripp
Summary: [FeFe]-hydrogenases are excellent H-2 evolution catalysts with active site cofactor comprising a [4Fe-4S] cluster linked to a diiron site with carbon monoxide and cyanide ligands. Proton transfer pathways and pH differences affect the stabilization of electrons at different cofactor states, influencing the hydrogen turnover process.
DALTON TRANSACTIONS
(2021)
Article
Nanoscience & Nanotechnology
U. Banin, N. Waiskopf, L. Hammarstrom, G. Boschloo, M. Freitag, E. M. J. Johansson, J. Sa, H. Tian, M. B. Johnston, L. M. Herz, R. L. Milot, M. G. Kanatzidis, W. Ke, I Spanopoulos, K. L. Kohlstedt, G. C. Schatz, N. Lewis, T. Meyer, A. J. Nozik, M. C. Beard, F. Armstrong, C. F. Megarity, C. A. Schmuttenmaer, V. S. Batista, G. W. Brudvig
Summary: This roadmap emphasizes the application of nanotechnology in addressing the challenges of energy conversion and focuses on solar energy conversion, including solar photovoltaics, solar water splitting, and bio-catalysis. Smart engineering design and semiconductor nanoparticles are utilized to improve solar-to-fuel conversion efficiency, while computational science is also meeting the challenges of nanomaterials synthesis.
Review
Chemistry, Multidisciplinary
Rhiannon M. Evans, Bhavin Siritanaratkul, Clare F. Megarity, Kavita Pandey, Thomas F. Esterle, Selina Badiani, Fraser A. Armstrong
CHEMICAL SOCIETY REVIEWS
(2019)