Post-transition state bifurcations on potential energy surfaces, where a single transition state structure leads to multiple products, have been known to exist for organic and biological reaction mechanisms for years, but recently, new reports of bifurcations have been occurring at a much higher rate. The newly discovered prevalence of bifurcations motivates computational chemists to develop techniques to understand what aspects of molecular structure and vibrations control the product selectivity in systems containing bifurcations. For example, the distribution of products seen in simulations has been found to be extremely sensitive to the local environment of the reacting system (i.e., the presence of a catalyst, enzyme, implicit or explicit solvent molecules). This specific study investigates a portion of the biosynthetic pathway to formation of a diterpene called abietadiene: specifically, the transformation of pimaradienyl cation to abietadienyl cation, which occurs in the class I active site of abietadiene synthase. This diterpene carbocation rearrangement involves a post-transition state bifurcation, which raises questions about the steering mechanism of the enzyme to form a single product in significantly larger amounts than other feasible side products. A variety of computational techniques have been used, including “theozymes” and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations performed within the class I active site of abietadiene synthase. This study aims to uncover the origin of two phenomena: (1) how this enzyme, abietadiene synthase, is altering this unique transformation compared to the inherent reactivity and (2) more generally, how the interaction between the energy distribution within a molecule and its surrounding environment causes certain chemical transformations to be physically viable and others not.

Control factors involved in abietadiene synthesis: A biosynthetic reaction containing a post-transition state bifurcation

254th National Meeting (2017)

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