Controlling monoterpene isomerization by guiding challenging carbocation rearrangement reactions in engineered squalene‐hopene cyclases

dc.contributor.authorLudwig, Julian
dc.contributor.authorCurado‐Carballada, Christian
dc.contributor.authorHammer, Stephan C.
dc.contributor.authorSchneider, Andreas
dc.contributor.authorDiether, Svenja
dc.contributor.authorKress, Nico
dc.contributor.authorRuiz‐Barragán, Sergi
dc.contributor.authorOsuna, Sílvia
dc.contributor.authorHauer, Bernhard
dc.date.accessioned2024-08-01T10:13:17Z
dc.date.available2024-08-01T10:13:17Z
dc.date.issued2024de
dc.date.updated2024-04-25T13:22:38Z
dc.description.abstractThe interconversion of monoterpenes is facilitated by a complex network of carbocation rearrangement pathways. Controlling these isomerization pathways is challenging when using common Brønsted 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 from Alicyclobacillus acidocaldarius (AacSHC) that catalyze the challenging isomerization of monoterpenes with unprecedented precision. Starting from a promiscuous isomerization of (+)‐β‐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 data suggest that 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.en
dc.description.sponsorshipHORIZON EUROPE European Research Councilde
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG)de
dc.description.sponsorshipGeneralitat de Catalunyade
dc.description.sponsorshipMinistry of science and innovationde
dc.description.sponsorshipHuman Frontier Science Program (HFSP)de
dc.identifier.issn1521-3773
dc.identifier.issn1433-7851
dc.identifier.other1897917805
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-147690de
dc.identifier.urihttp://elib.uni-stuttgart.de/handle/11682/14769
dc.identifier.urihttp://dx.doi.org/10.18419/opus-14750
dc.language.isoende
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/679001de
dc.relation.uridoi:10.1002/anie.202318913de
dc.rightsinfo:eu-repo/semantics/openAccessde
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/de
dc.subject.ddc540de
dc.titleControlling monoterpene isomerization by guiding challenging carbocation rearrangement reactions in engineered squalene‐hopene cyclasesen
dc.typearticlede
ubs.fakultaetChemiede
ubs.fakultaetFakultätsübergreifend / Sonstige Einrichtungde
ubs.institutInstitut für Biochemie und Technische Biochemiede
ubs.institutFakultätsübergreifend / Sonstige Einrichtungde
ubs.publikation.seiten11de
ubs.publikation.sourceAngewandte Chemie International edition 63 (2024), No. e202318913de
ubs.publikation.typZeitschriftenartikelde

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
ANIE_ANIE202318913.pdf
Size:
2.28 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
3.3 KB
Format:
Item-specific license agreed upon to submission
Description: