title: Structural basis of enzymatic benzene ring reduction.
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.
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weinert
authors.affiliation: Microbiology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Simona G
authors.initials: SG
authors.lastname: Huwiler
authors.affiliation: Microbiology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Kung
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Weidenweber
authors.affiliation: Laboratoire de Bioélectrochimie et Spectroscopie, UMR 7140, Chimie de la Matière Complexe, Université de Strasbourg-CNRS, Strasbourg, France.
authors.forename: Petra
authors.initials: P
authors.lastname: Hellwig
authors.affiliation: Department of Analytical Chemistry, Helmholtz Centre for Environmental Research UFZ, Leipzig, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Stärk
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Biskup
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.affiliation: 1] Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. [2] Canadian Light Source, Saskatoon, Saskatchewan, Canada.
authors.forename: Julien J H
authors.initials: JJ
authors.lastname: Cotelesage
authors.affiliation: Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
authors.affiliation: Max Planck Institute of Biophysics, Frankfurt, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
authors.affiliation: Microbiology, Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Boll
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D001554:Benzene / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D001673:Biodegradation, Environmental; D018360:Crystallography, X-Ray; D004579:Electron Transport; D004583:Electrons; D004785:Environmental Pollutants / Q000737:chemistry* / Q000378:metabolism; D045302:Geobacter / Q000737:chemistry* / Q000201:enzymology; D007700:Kinetics; D008958:Models, Molecular; D010084:Oxidation-Reduction; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D011522:Protons; D013379:Substrate Specificity; D014414:Tungsten / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D004785:Environmental Pollutants; D011522:Protons; C037817:benzoyl-coenzyme A; D044925:Oxidoreductases Acting on CH-CH Group Donors; C109030:benzoyl-coenzyme A reductase (dearomatizing); D015032:Zinc; D001554:Benzene; D014414:Tungsten