Why does the enzyme SyrB2 chlorinate, but does not hydroxylate, saturated hydrocarbons? A density functional theory (DFT) study

Syringomycin halogenase (SyrB2) is a non-heme Fe(II)/alpha-ketoglutarate (alphaKG)-dependent enzyme which catalyses halogenation of saturated hydrocarbons, but unlike other closely related enzymes, does not catalyse the corresponding hydroxylation reaction. We have carried out density functional theory (DFT) calculations to try to understand this specificity. Calculations which include only the basic six coordinate iron centre suggest that both hydroxylation and halogenation are feasible by a rebound mechanism. We suggest that the hydroxylation reaction is inhibited by protonation of the hydroxo intermediate, leading to only chlorination. We propose that this hypothesis could be tested using a mutant enzyme.