Structural basis of enzymatic benzene ring reduction

• Published in: Nature chemical biology Vol. 11; no. 8; pp. 586 - 591
• Main Authors: Weinert, Tobias, Huwiler, Simona G, Kung, Johannes W, Weidenweber, Sina, Hellwig, Petra, Stärk, Hans-Joachim, Biskup, Till, Weber, Stefan, Cotelesage, Julien J H, George, Graham N, Ermler, Ulrich, Boll, Matthias
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2015
• Subjects: Acyl Coenzyme A - chemistry; Acyl Coenzyme A - metabolism; Alkali metals; Ammonia; Aromatic compounds; Bacterial Proteins - chemistry; Bacterial Proteins - isolation & purification; Bacterial Proteins - metabolism; Benzene; Benzene - chemistry; Benzene - metabolism; Biocatalysis; Biocatalysts; Biodegradation, Environmental; Biomimetics; Chemical Sciences; Chemical synthesis; Crystallography, X-Ray; Electron Transport; Electrons; Environmental Pollutants - chemistry; Environmental Pollutants - metabolism; Enzymes; Geobacter - chemistry; Geobacter - enzymology; Kinetics; Models, Molecular; or physical chemistry; 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; Redox potential; Solvents; Substrate Specificity; Theoretical and; Tungsten; Tungsten - chemistry; Tungsten - metabolism; Zinc - chemistry; Zinc - metabolism; Spectroélectrochimie; Électrochimie; Chimie Physique; Spectroscopie
• ISSN: 1552-4450; 1552-4469; 1552-4469
• DOI: 10.1038/nchembio.1849

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.