Structural basis of enzymatic benzene ring reduction

Tobias Weinert; Simona G Huwiler; Johannes W Kung; Sina Weidenweber; Petra Hellwig; Hans-Joachim Stärk; Till Biskup; Stefan Weber; Julien J H Cotelesage; Graham N George; Ulrich Ermler; Matthias Boll

doi:10.1038/nchembio.1849

Structural basis of enzymatic benzene ring reduction

Nat Chem Biol. 2015 Aug;11(8):586-91. doi: 10.1038/nchembio.1849. Epub 2015 Jun 29.

Authors

Affiliations

¹ Max Planck Institute of Biophysics, Frankfurt, Germany.
² Microbiology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
³ Laboratoire de Bioélectrochimie et Spectroscopie, UMR 7140, Chimie de la Matière Complexe, Université de Strasbourg-CNRS, Strasbourg, France.
⁴ Department of Analytical Chemistry, Helmholtz Centre for Environmental Research UFZ, Leipzig, Germany.
⁵ Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
⁶ 1] Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. [2] Canadian Light Source, Saskatoon, Saskatchewan, Canada.
⁷ Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

PMID: 26120796
DOI: 10.1038/nchembio.1849

Abstract

In chemical synthesis, the widely used Birch reduction of aromatic compounds to cyclic dienes requires alkali metals in ammonia as extremely low-potential electron donors. An analogous reaction is catalyzed by benzoyl-coenzyme A reductases (BCRs) that have a key role in the globally important bacterial degradation of aromatic compounds at anoxic sites. Because of the lack of structural information, the catalytic mechanism of enzymatic benzene ring reduction remained obscure. Here, we present the structural characterization of a dearomatizing BCR containing an unprecedented tungsten cofactor that transfers electrons to the benzene ring in an aprotic cavity. Substrate binding induces proton transfer from the bulk solvent to the active site by expelling a Zn(2+) that is crucial for active site encapsulation. Our results shed light on the structural basis of an electron transfer process at the negative redox potential limit in biology. They open the door for biological or biomimetic alternatives to a basic chemical synthetic tool.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acyl Coenzyme A / chemistry
Acyl Coenzyme A / metabolism
Bacterial Proteins / chemistry*
Bacterial Proteins / isolation & purification
Bacterial Proteins / metabolism
Benzene / chemistry*
Benzene / metabolism
Biocatalysis
Biodegradation, Environmental
Crystallography, X-Ray
Electron Transport
Electrons*
Environmental Pollutants / chemistry*
Environmental Pollutants / metabolism
Geobacter / chemistry*
Geobacter / enzymology
Kinetics
Models, Molecular
Oxidation-Reduction
Oxidoreductases Acting on CH-CH Group Donors / chemistry*
Oxidoreductases Acting on CH-CH Group Donors / isolation & purification
Oxidoreductases Acting on CH-CH Group Donors / metabolism
Protons
Substrate Specificity
Tungsten / chemistry
Tungsten / metabolism
Zinc / chemistry
Zinc / metabolism

Substances

Acyl Coenzyme A
Bacterial Proteins
Environmental Pollutants
Protons
benzoyl-coenzyme A
Oxidoreductases Acting on CH-CH Group Donors
benzoyl-coenzyme A reductase (dearomatizing)
Zinc
Benzene
Tungsten

Associated data

PDB/4Z3W
PDB/4Z3X
PDB/4Z3Y
PDB/4Z3Z
PDB/4Z40

Grants and funding

Canadian Institutes of Health Research/Canada