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.

Structure and Function of the Unusual Tungsten Enzymes Acetylene Hydratase and Class II Benzoyl-Coenzyme A Reductase

“…The fifth ligand is a sulfhydryl sulfur of a highly conserved cysteine that is missing in AORs; it, therefore, serves as a distinguishing marker of class II BCRs. A sixth inorganic ligand of the W atom was identified, the nature of which is still unclear [Weinert et al, 2015]. The electron density maps obtained from X-ray structure analysis argue against monoatomic C/N/O ligands, and are in favour of an electron-rich sulfur or chloride ligand ( fig.…”

“…The structure of the Bam(BC) 2 heterotetramer was recently solved by X-ray crystallography in the as-isolated Zn aerobically grown protein crystals [Weinert et al, 2015]. The Bam(BC) 2 -CoA-ester complex structures are essentially identical at the current resolution and therefore treated as one structural state.…”

“…The two-electron redox reactions normally involve oxo-or hydroxo transfer with the substrate or product being directly coordinated to the Mo/W via an oxygen atom [Hille, 2013;Pushie et al, 2014]. The only exceptions appear to be Wcontaining BCRs, which contain an occupied W ligation shell without the option of additional substrate or product binding [Weinert et al, 2015].…”

An unusual strategy for the anoxic biodegradation of phthalate

“…In the past two decades, the enzymes involved in these reactions have been studied in vitro to some detail, many of which follow unprecedented enzymatic principles (Figure 1; for recent reviews see Carmona et al, 2009;Fuchs et al, 2011;Philipp and Schink, 2012;Boll et al, 2014;Buckel et al, 2014). Benzoyl-CoA is finally dearomatized to a conjugated dienoyl-CoA either by ATP-dependent (Boll and Fuchs, 1995) or ATP-independent (Weinert et al, 2015) benzoyl-CoA reductases. In spite of the insights obtained in the oxygen-independent biomineralization of most environmentally relevant monocyclic aromatics, the anaerobic degradation of phthalate (1,2-dicarboxybenzene) has remained largely unknown.…”

Environment-Friendly Reduction of Aromatics to Alicyclic Compounds at Room Temperature Using Superactive Calcined Ni-Al Hydrotalcite Catalysts

“…For the mixed oxides, the presence of some Ni 2+ ions in tetrahedral holes, together with Ni 2+ in octahedral ones, and of Ni 3+ species in the oxides obtained by calcination at 550°C are responsible for the intense background and intense charge transfer band in the ultraviolet region" [20]. The UV-vis spectra of the microwave-hydrothermally treated samples show that Ni ions recovered their original location in octahedral holes, and that this relocation is complete after a 300 min treatment [24,27,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Samples of Ni-Al 2.5: 1 HT showed the band at lower wavelength almost disappearing and the broad absorption due to Ni 3+ ions is almost negligible; actually, the sample recovered its original green colour.…”