Gordeev Evgeniy G, Ananikov Valentine P
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, Moscow, Russia.
PLoS One. 2015 Apr 8;10(4):e0119984. doi: 10.1371/journal.pone.0119984. eCollection 2015.
A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.
通过在密度泛函（B3LYP、O3LYP、M062X）和半经验水平（PM6-DH2、PM6）上对一个模型系统进行理论计算，研究了与酶催化的[4+2]环加成反应相关的一种可能的机理途径。在一个模型反应中考虑多杀菌素A的酶催化生物合成，对关键的[4+2]环加成步骤进行了计算，实验报道了该反应是生物狄尔斯-阿尔德反应的一个可靠实例。在本研究中表明，[4+2]环加成反应可能受益于沿着能量平衡的反应坐标进行，这使得涉及单一过渡态的[4+2]环加成途径的催化速率得以提高。对这样一个由三个氨基酸配位的系统进行建模表明，与非催化转化相比，活化能可靠地降低了约18.0千卡/摩尔。
