Jaden Webb

Nature’s First Step of Rotenone Biosynthesis: Conversion of L-Phenylalanine to trans-Cinnamic Acid

Jaden T. Webb, Missouri State University

Co-Author: Matthew R. Siebert, Missouri State University

Rotenone, a naturally occurring substance in the rotenoid family, was once used as a pesticide and piscicide. Its use was banned in the US due to an alarming realization: geographical areas that used rotenone showed an increased rate of Parkinson’s disease. The cause of Parkinson’s is not yet understood, but understanding how nature produces rotenone may help lead us toward an answer.

Rotenone is naturally synthesized in plants from the amino acid L-phenylalanine. The conversion of L-phenylalanine to trans-cinnamic acid is the first step in the biosynthesis of rotenone; understanding how this happens is the focus of the project. This reaction is thought to occur through an E1_cb elimination reaction. However, E1 and E2 elimination reactions are also viable options. Gaussian16 was used to computationally evaluate E1, E2, and E1_cb possibilities. Thus far, most energy points along the reaction pathway for each reaction have been located. The energy diagrams of the elimination reactions represent what we would expect to see in the conversion of L-phenylalanine to trans-cinnamic acid. These energy calculations allow for determination of the thermodynamic preferences of each possible mechanism.

From this point, we plan to find the remaining values for the reaction coordinates; these values will help us further assess the mechanism. Understanding the first step in the long pathway to forming rotenone may be the information we need to understand Parkinson’s disease.