title: Computational study of a model system of enzyme-mediated [4+2] cycloaddition reaction.
abstract: 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.
authors: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, Moscow, Russia.
authors: Evgeniy G
authors: EG
authors: Gordeev
authors: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, Moscow, Russia.
authors: Valentine P
authors: VP
authors: Ananikov
mesh_terms: D055162:Biocatalysis; D061565:Cycloaddition Reaction; D004798:Enzymes / Q000378:metabolism*; D006860:Hydrogen Bonding; D018942:Macrolides / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D018942:Macrolides; C114883:spinosyn A