A comparative DFT study of substrates and products of industrial enzyme nitrile hydratase

Nitrile hydratase (NHase) is a metalloenzyme used in industrial biotechnology for a large scale production of common chemicals. NHases convert nitriles to the corresponding amides. Although the structures of some forms of NHases containing nonheme low spin Fe(III) or low spin noncorrinoid Co(III) are known, neither a catalytic mechanism nor the reasons of high selectivity towards aromatic ligands are recognized. Optimized geometries, molecular electrostatic potential maps and infrared spectra of commercially important aromatic substrates of the NHase (nicotinonitrile, o‐, m‐, p‐methylbenzonitrile) and the corresponding products (nicotinamide, o‐, m‐, p‐methylbenzamid) were investigated using the density functional theory method with the B3LYP functional and the 6‐31G(d,p) basis set. Calculated hypothetical intrinsic reaction paths indicate that benzimidic acids may be involved as intermediates. This study elucidates differences in the electronic properties of substrates and products of NHases, provides an insight into the molecular basis of the catalytic reaction and helps to explain varying enzymatic activities of microbial NHases. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008