S10: Dehalogenating and dearomatizing halobenzoyl-CoA reductases

Benzoyl-CoA reductases are key enzymes in the degradation of aromatic compounds in anaerobic bacteria. They catalyze the two-electron reduction of benzoyl-CoA to cyclohexa-1,5-dienoyl-CoA. A radical mechanism via single electron transfer steps according to the Birch reduction in organic synthesis has been proposed for this reaction. E°’ of the two-electron reduction is –622 mV; as this redox potential is far below any physiological reductant, the reaction needs to be coupled to an exergonic reaction. Class I benzoyl-CoA reductases contain [4Fe-4S] clusters and couple electron transfer to a stoichiometric ATP-hydrolysis. In contrast, the W-containing class II benzoyl-CoA reductases are proposed to overcome the high redox barrier by an electron bifurcation process. Class I benzoyl-CoA reductases were recently found to catalyze an unprecedented reductive dehalogenation reaction: the reductive dehalogenation of 3-chloro-/3-bromobenzoyl-CoA to benzoyl-CoA. A two-step dearomatization/HCl-elimination mechanism has been proposed. 3-F-benzoyl-CoA was dearomatized to 3-F-1,5-dienoyl-CoA without HF-elimination. Preliminary results indicate that class II benzoyl-CoA reductases have also the capacity for reductive halobenzoyl-CoA dehalogenation. The mechanism of reductive dehalogenation by benzoyl-CoA reducrases differs fundamentally from the mechanism of the corrinoid-containing reductive dehalogenases involved in organohalide respiration. It represents a novel mode of enzymatic dehalogenation that may be used for applied synthetic purposes.