A Theoretical Study on the Mechanism of Decarboxylations for Hydroxymandelate Synthase

Hydroxymandelate synthase is one type of alpha-keto acid-dependent oxygenases and plays an important role in the biosynthesis of hydroxyphenyl-pyruvate. The ferrous and ferryl intermediates in the reaction were considered to be very important in the DNA repair process. The mechanism of hydroxymandelate synthase was investigated by a theoretical method based on B3LYP/LACVP*. The data indicated that each decarboxylation went through a process of direct dioxygen insertion. The first oxidative decarboxylation experienced only one transition state, while there were two potential pathways for the second decarboxylation process. The calculation data showed that the stepwise one was favored to the concerted one due to the lower energy barrier. The process to form the iron-superoxide was the rate-limiting step. After two consecutive decarboxylations, a proton transfer reaction was needed to obtain the target products. Two possible transition states were found out to achieve this step. The one with a six-membered ring structure was preferred because of the lower activation energy. In addition, several ferryl species with high spins were captured in the whole process, which could be supplied as requisite substrates for DNA repair reaction.