Enzymatic Birch reduction via hydrogen atom transfer at [4Fe-4S]-OH2 and [8Fe-9S] clusters

Jonathan Fuchs, Unai Fernández-Arévalo, Ulrike Demmer, Eduardo Díaz, G. Matthias Ullmann, Antonio J. Pierik, Ulrich Ermler and Matthias Boll ()
Additional contact information
Jonathan Fuchs: University of Freiburg
Unai Fernández-Arévalo: Centro de Investigaciones Biológicas Margarita Salas-CSIC
Ulrike Demmer: Max Planck Institute of Biophysics
Eduardo Díaz: Centro de Investigaciones Biológicas Margarita Salas-CSIC
G. Matthias Ullmann: University of Bayreuth
Antonio J. Pierik: RPTU Kaiserslautern-Landau
Ulrich Ermler: Max Planck Institute of Biophysics
Matthias Boll: University of Freiburg

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract The alkali metal- and ammonia-dependent Birch reduction is the classical synthetic method for achieving dihydro additions to arenes, typically yielding 1,4-cyclodienes. A mild biological alternative to this process are 1,5-dienoyl-coenzyme A (CoA)-forming class I and II benzoyl-CoA reductases (BCRs), widely abundant key enzymes in the biodegradation of aromatic compounds at anoxic environments. To obtain a comprehensive mechanistic understanding of class I BCR catalysis, we produced the active site subunits from a denitrifying bacterium and determined the X-ray structure of its substrate and product complexes at 1.4 Å revealing non-canonical double-cubane [8Fe-9S] and active site aqua-[4Fe-4S] clusters. Together with kinetic, spectroscopic and QM/MM studies, we provide evidence for a radical mechanism with a [4Fe-4S] cluster-bound water molecule acting as hydrogen atom and electron donor at potentials beyond the biological redox window. An analogous Birch-like radical mechanism is applied by class II BCRs with the catalytic water bound to a tungsten-bis-metallopterin cofactor. The use of activated, metal-bound water ligands as hydrogen atom donor serves as a basic blueprint for future enzymatic or biomimetic Birch reduction processes.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58418-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58418-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58418-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().