Evidence map›Paper›PMID 41852202›Full record

ArticleFEBS letters2026

A methionine-lined active site governs carbocation stabilization and product specificity in a bacterial terpene synthase.

Marion Ringel, Carl P O Helmer, Shani Zev, Ronja Driller, Emily Buhr, Markus Reinbold, Renana Schwartz, Gabriel Foley, Mikael Boden, Daniel Garbe and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FEBS letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Marion RingelWerner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), TUM School of Natural Sciences, Garching, Germany.ORCID https://orcid.org/0000-0003-0162-0765
Carl P O HelmerInstitute of Chemistry and Biochemistry, Laboratory of Structural Biochemistry, Freie Universität Berlin, Germany.ORCID https://orcid.org/0000-0001-7195-9938
Shani ZevDepartment of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.
Ronja DrillerInstitute of Chemistry and Biochemistry, Laboratory of Structural Biochemistry, Freie Universität Berlin, Germany.ORCID https://orcid.org/0000-0001-8834-9087
Emily BuhrWerner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), TUM School of Natural Sciences, Garching, Germany.
Markus ReinboldWerner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), TUM School of Natural Sciences, Garching, Germany.
Renana SchwartzDepartment of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.
Gabriel FoleySchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Mikael BodenSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Daniel GarbeWerner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), TUM School of Natural Sciences, Garching, Germany.
Gerhard SchenkSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Dan Thomas MajorDepartment of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.ORCID https://orcid.org/0000-0002-9231-0676
Bernhard LollInstitute of Chemistry and Biochemistry, Laboratory of Structural Biochemistry, Freie Universität Berlin, Germany.ORCID https://orcid.org/0000-0001-7928-4488
Thomas BrückWerner Siemens-Chair of Synthetic Biotechnology, Technical University of Munich (TUM), TUM School of Natural Sciences, Garching, Germany.ORCID https://orcid.org/0000-0002-2113-6957

Funding

Bundesministerium für Bildung und Forschung 031A276AChristiane Nüsslein-Volhard-StiftungDeutsche Forschungsgemeinschaft RTG 2473-1German-Israeli Foundation for Scientific Research and Development I-85-302.14-2018Hanns-Seidel-StiftungMinistry of Culture and Sport 3-16310Werner Siemens-Stiftung
6 · The paper itself

Abstract

Terpene synthases (TPSs) generate complex hydrocarbon scaffolds through carbocationic cyclization cascades that demand precise active-site control to stabilize reactive intermediates. While π-cation and electrostatic interactions are established stabilizing factors, the role of methionine has remained unclear. Here, we identify a methionine-rich active site in hydropyrene synthase (HpS), a bacterial Class I TPS involved in pseudopterosin biosynthesis. Crystallography, mutagenesis, and multiscale QM/MM simulations reveal that methionine residues provide steric guidance and direct sulfur-carbocation stabilization during catalysis. Mutations alter product distributions, confirming functional relevance. Quantum chemical calculations indicate that sulfur-carbocation interactions are energetically comparable to π-carbocation interactions. These results uncover a previously unrecognized mechanism of carbocation stabilization in terpene biosynthesis.

Indexed as

Alkyl and Aryl TransferasesBacterial ProteinsMethionineCatalytic DomainCrystallography, X-RayMolecular Dynamics SimulationSubstrate SpecificityAlkyl and Aryl TransferasesBacterial ProteinsMethionineterpene synthasebiocatalysiscarbocationgreen chemistryMD simulationterpeneX‐ray crystallography

Identifiers

PMID41852202
PMCPMC13244428

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.