Fluoroacetate dehalogenase catalyzed dehalogenation of halogenated carboxylic acids: A QM/MM approach

Dehalogenation is one of the most important reactions in environmental pollution control, for instance, the degradation of persistent organic pollutants (POPs). Recently, fluoroacetate dehalogenase (FAcD) has been reported to catalyze the dehalogenation reactions, which shows great potential in treating halogenated pollutants. Here the dehalogenation mechanism catalyzed by FAcD was fully deciphered with the aid of quantum mechanics/molecular mechanics method. The results show that FAcD catalyzed dehalogenation efficiency follows the order of defluorination > dechlorination > debromination. The corresponding Boltzmann-weighted average barriers are 10.1, 19.7, and 20.9 kcal mol-1. Positive/negative correlations between activation barriers and structural parameters (e.g. distance and angle) for FAcD catalyzed dechlorination and debromination were established. Based on the structure-energy relationship, we propose that mutation of the binding pocket amino acids (e.g. His155, Trp156, Tyr219) to smaller proton donor amino acids (e.g. Serine, Threonine, Cysteine, Asparagine) may increase the efficiency for dechlorination and debromination. The results may of practical value for the efficient degradation of chlorined and bromined pollutants by harnessing FAcD.