N,N-Dimethyltryptamine (DMT) is a powerful psychedelic that induces temporary serotonergic and psychedelic effects on the human brain. DMT is a structural analog of serotonin that has been shown to act as an agonist on the serotonin receptors in the brain. It is currently being studied as a potential treatment for neurological disorders such as PTSD, depression, and anxiety. With further studies, psychedelic drugs could become a future treatment for these common disorders. This project entails the biosynthesis of DMT derivatives created from the combination of serine and diverse indoles using the native E. coli tryptophan synthase (TrpB) to form tryptophan derivatives, which are then decarboxylated using the Psilocybe cubensis decarboxylase PsiD to create tryptamine derivatives, and lastly methylated twice by a cane toad N-methyltransferase to form DMT derivatives. These newly synthesized DMT derivatives have single-substituted side chains at various positions on the backbone structure which correspond to the substitutions from the corresponding indoles provided in the culture media. The fermentation samples are analyzed by HPLC (High Performance Liquid Chromatography) and LC-MS (Liquid Chromatography-Mass Spectrometry) to confirm and quantify the DMT derivative production. By testing diverse indoles substituted at different positions, there will be further insight as to which positions and indoles process better to produce higher yields of DMT derivatives using this system. This ultimately provides a library of single-substituted DMT derivatives which can be made available for other researchers to study in their model system of choice.
Author(s): Niya B. Fried, William J. Gibbons Jr., J. Andrew Jones
Mentor:J. Andew Jones, Department of Chemical, Paper, and Biomedical Engineering
William J. Gibbons Jr., Department of Chemical, Paper, and Biomedical Engineering
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