Mechanistic Studies on the Decoupled Desaturation and Epoxidation Catalyzed by AsqJ Enzyme

【作者】 苏浩； 刘永军；

【机构】 山东大学理论化学研究所；

【摘要】 Here,we performed a QM/MM studies to explore both the desaturation and epoxidation processes of AsqJ enzyme from Aspergillus nidulans,which have been proposed to be a dioxygenase.[1]The ground state of the Fe~Ⅳ-oxo is quintet state,and the following reaction occurs on the quintet state surface.The Fe~Ⅳ-oxo should firstly undergo an isomerization to initiate the reactions.In the desaturation process,the abstraction of the first hydrogen follows the σ-channel mechanism,which is the rate-limiting step with an energy barrier of 19.3 kcal/mol.The second hydrogen atom abstraction is calculated to be quite easy.In epoxidation reaction,the regenerated Fe~Ⅳ-oxo species attacks on the C=C bond of the desaturated intermediate to form a carbon-based radical intermediate,then the final product of AsqJ is formed via a ring closure with a barrier of 3.9 kcal/mol.Besides,calculations using the substrate without N4-methyl reveal that the H-abstraction by Fe~Ⅳ-oxo is still accessible,which suggests that the absence of N4-methyl does not affect the desaturation process itself,but may influence the other processes which are prior to the desaturation process.更多还原

【Abstract】 Here,we performed a QM/MM studies to explore both the desaturation and epoxidation processes of AsqJ enzyme from Aspergillus nidulans,which have been proposed to be a dioxygenase.[1]The ground state of the Fe~Ⅳ-oxo is quintet state,and the following reaction occurs on the quintet state surface.The Fe~Ⅳ-oxo should firstly undergo an isomerization to initiate the reactions.In the desaturation process,the abstraction of the first hydrogen follows the σ-channel mechanism,which is the rate-limiting step with an energy barrier of 19.3 kcal/mol.The second hydrogen atom abstraction is calculated to be quite easy.In epoxidation reaction,the regenerated Fe~Ⅳ-oxo species attacks on the C=C bond of the desaturated intermediate to form a carbon-based radical intermediate,then the final product of AsqJ is formed via a ring closure with a barrier of 3.9 kcal/mol.Besides,calculations using the substrate without N4-methyl reveal that the H-abstraction by Fe~Ⅳ-oxo is still accessible,which suggests that the absence of N4-methyl does not affect the desaturation process itself,but may influence the other processes which are prior to the desaturation process.更多还原