Mechanism of fatty acid decarboxylation catalyzed by a non-heme iron oxidase (UndA): a QM/MM study

UndA is a non-heme iron enzyme that was recognized to catalyze the decarboxylation of medium chain (C10-C14) fatty acids to produce trace amounts of 1-alkenes. Owing to the electron imbalance during the oxidative decarboxylation of the substrate and the reduction of O-2, only single turnover reactions were obtained in UndA in vitro assays. Unlike the general non-heme iron enzymes, the catalytic efficiency of UndA is quite low. According to the previous proposal, both Fe-III-OO- and (FeO)-O-IV complexes may abstract the beta-H of fatty acids to trigger the oxidative decarboxylation reaction. Herein, on the basis of the crystal structures of UndA in complex with the substrate analogues, we constructed a series of computational models and performed quantum mechanics/molecular mechanics (QM/MM) calculations to explore the UndA-catalyzed decarboxylation using lauric acid as the substrate. Our calculation results reveal that only the Fe-III-OO- complex can initiate the decarboxylation, and the substrate (lauric acid) should monodentately coordinate to the Fe center to facilitate the beta-H abstraction. In addition, the monodentate coordination corresponds to higher relative energy than the bidentate mode, which may explain the low efficiency of UndA. It is also revealed that as long as the beta-H is extracted by the Fe-III-OO-, the decarboxylation of the substrate radical is quite easy, and an electron transfer from the substrate to the iron center is the prerequisite. For the (FeO)-O-IV complex, since the beta-H is far from the O-Fe atom and the angle of angle Fe-O-H is 53.1 degrees, the H-abstraction is calculated to be difficult.