Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases
Ludwig J, Curado-Carballada C, Hammer S, Schneider A, Diether S, Kress N, Ruiz-Barragán S, Osuna S, Hauer B (2024)
Angewandte Chemie International Edition 63(12): e202318913.
Zeitschriftenaufsatz
| E-Veröff. vor dem Druck | Englisch
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Autor*in
Ludwig, Julian;
Curado-Carballada, Christian;
Hammer, StephanUniBi ;
Schneider, Andreas;
Diether, Svenja;
Kress, Nico;
Ruiz-Barragán, Sergi;
Osuna, Silvia;
Hauer, Bernhard
Einrichtung
Abstract / Bemerkung
The interconversion of monoterpenes is facilitated by a complex network of carbocation rearrangement pathways. Controlling these isomerization pathways is challenging when using common Bronsted and Lewis acid catalysts, which often produce product mixtures that are difficult to separate. In contrast, natural monoterpene cyclases exhibit high control over the carbocation rearrangement reactions but are reliant on phosphorylated substrates.In this study, we present engineered squalene-hopene cyclases fromAlicyclobacillus acidocaldarius(AacSHC) that catalyze the challenging isomerization of monoterpenes with unprecedented precision.Starting from a promiscuous isomerization of (+)-beta-pinene, we first demonstrate noticeable shifts in the product distribution solely by introducing single point mutations. Furthermore, we showcase the tuneable cation steering by enhancing (+)-borneol selectivity from 1% to >90% (>99%de) aided by iterative saturation mutagenesis. Our combined experimental and computational datasuggeststhat the reorganization of key aromatic residues leads to the restructuring of the water network that facilitates the selective termination of the secondary isobornyl cation. This work expands our mechanistic understanding of carbocation rearrangements and sets the stage for target-oriented skeletal reorganization of broadly abundant terpenes. © 2024 Wiley-VCH GmbH.
Stichworte
Biocatalysis;
Brønsted Acid Catalysis;
Secondary Carbocations;
Terpenoids;
Sustainable Chemistry
Erscheinungsjahr
2024
Zeitschriftentitel
Angewandte Chemie International Edition
Band
63
Ausgabe
12
Art.-Nr.
e202318913
Urheberrecht / Lizenzen
eISSN
1521-3773
Page URI
https://pub.uni-bielefeld.de/record/2986505
Zitieren
Ludwig J, Curado-Carballada C, Hammer S, et al. Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases. Angewandte Chemie International Edition. 2024;63(12): e202318913.
Ludwig, J., Curado-Carballada, C., Hammer, S., Schneider, A., Diether, S., Kress, N., Ruiz-Barragán, S., et al. (2024). Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases. Angewandte Chemie International Edition, 63(12), e202318913. https://doi.org/10.1002/anie.202318913
Ludwig, Julian, Curado-Carballada, Christian, Hammer, Stephan, Schneider, Andreas, Diether, Svenja, Kress, Nico, Ruiz-Barragán, Sergi, Osuna, Silvia, and Hauer, Bernhard. 2024. “Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases”. Angewandte Chemie International Edition 63 (12): e202318913.
Ludwig, J., Curado-Carballada, C., Hammer, S., Schneider, A., Diether, S., Kress, N., Ruiz-Barragán, S., Osuna, S., and Hauer, B. (2024). Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases. Angewandte Chemie International Edition 63:e202318913.
Ludwig, J., et al., 2024. Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases. Angewandte Chemie International Edition, 63(12): e202318913.
J. Ludwig, et al., “Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases”, Angewandte Chemie International Edition, vol. 63, 2024, : e202318913.
Ludwig, J., Curado-Carballada, C., Hammer, S., Schneider, A., Diether, S., Kress, N., Ruiz-Barragán, S., Osuna, S., Hauer, B.: Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases. Angewandte Chemie International Edition. 63, : e202318913 (2024).
Ludwig, Julian, Curado-Carballada, Christian, Hammer, Stephan, Schneider, Andreas, Diether, Svenja, Kress, Nico, Ruiz-Barragán, Sergi, Osuna, Silvia, and Hauer, Bernhard. “Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene-Hopene Cyclases”. Angewandte Chemie International Edition 63.12 (2024): e202318913.
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