Computational insights into the oxidation of mono- and 1,4 disubstituted arenes by the Toluene Dioxygenase enzymatic complex

Publication date: Available online 8 March 2017 Source:Journal of Molecular Catalysis B: Enzymatic Author(s): Ma. Agustina Vila, Diego Umpiérrez, Gustavo Seoane, Sonia Rodríguez, Ignacio Carrera, Nicolás Veiga Toluene Dioxygenase (TDO) enzymatic complex has been widely used for preparation of enantiopure cis-cyclohexadienediols for synthetic applications. Along the last 30 years, a variety of mono- and di-substituted arenes have been studied as substrates for this enzyme, and some interesting observations have been reported regarding the yield and selectivity of the biotransformation. Nevertheless, none of them has been explained considering the active site’ structural and electronic features. In this work we present the first computational model of TDO’s active site, with a description of its architecture and interactions with the substrate to understand and predict substrate orientation. Our findings indicate that in the O2-free TDO, the iron(II) is stabilized by the coordination of an oxygen atom from the neighboring Gln215 residue. Besides, the active site is comprised by four pockets with different relative affinities for the substrates’ substituents. Monosubstituted arenes adopt a pose in which the alkyl chains maximize the London dispersion interactions with minimal steric clashes, giving an explanation for the observed trend in the benzylic hydroxylation yields. Finally, the computational results allowed us to rationalize the enantiomeric excess of 1,...

Source: Journal of Molecular Catalysis B: Enzymatic - March 8, 2017 Category: Biochemistry Source Type: research