Maciej Szaleniec
Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Krakow, Poland - Research
Tungsten-containing enzymes – new tools in the biotech toolbox. Modelling and challenges.
Maciej Szaleniec1, Victor Baerle1, Tommaso Attuci2, Claudia Andreini2, Johann Heider3 1Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland; 2Department of Chemistry, University of Florence, Italy; 3Faculty of Biology, Philipps-Universität Marburg, Marburg, Germany
Abstract
The incorporation of tungsten pterin complexes into the active site of enzymes enormously expands the available repertoire of possible chemical transformations. The central metal facilitates two-electron redox processes due to stable IV and VI oxidation states and acts as a Lewis acid (with its open ligation position), which can directly activate a bound reagent. Meanwhile, the other ligands of the W ions participate in the reactions by (i) providing additional means to activate recalcitrant bonds (e.g. in homo or heterolytic C-H cleavage), (ii) enabling hydroxylations without molecular oxygen (by O transfer to activated intermediates), (iii) introducing strong acid/base catalysis (accepting protons or enabling proton transfer electron transfer processes), (iv) tuning the W redox potentials by varying their positions, or (v) even participate directly in the redox processes by providing a reservoir for additional electrons. Moreover, many W-enzymes contain additional redox-active cofactors assembling into “nanowire” structures, which connect the W-cofactors with other active sites within the enzyme. As a result, many chemically highly challenging reactions are catalysed by W-enzymes, such as direct reduction of aromatic rings, reduction of CO2 to formate or of non-activated carboxylic acids to aldehydes, hydroxylation of alkylaromatic or heterocyclic compounds, hydration of acetylene to acetaldehyde, or oxidation of molecular hydrogen. In the presentation, we will show our recent results on parametrization of the AMBER force field for the tungsten cofactor, as well as highlight several challenges that make this process difficult. Furthermore, we will present our latest results on QM-modelling of the reaction pathway for aldehyde oxidoreductase from Aromatoleum aromaticum, that not only is able to oxidise aldehydes but also molecular hydrogen. We will highlight the problem with establishing the oxidation state and the coordination mode of the heavy metal by structural techniques, as well as the oxidation states of the metallopterin cofactor. We will also present our working hypothesis on the activation of molecular hydrogen by the W-cofactor.
Acknowledgement
The authors acknowledge the partial financial support of the Polish National Science Centre (OPUS26 2023/51/B/ST4/01224) and the European Union’s HORIZON-EIC-2023- PATHFINDEROPEN-01 under grant agreement No 101129798, European Innovation Council Pathfinder project W-BioCat, as well as financial support of high-performance computing infrastructure PL-Grid (HPC Centers: ACK Cyfronet AGH, grants PLG/2021/014761, PLG/2023/016443, PLG/2024/017327, and PLG/2025/018449).
