Metabolic Engineering
June 14, 2026
Zachary N. Abrahms, Mohammad Majdi, Siena M. Madsen et al.
Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to integrate and rebalance multigene...
Current Opinion in Biotechnology
May 15, 2025
Zachary N. Abrahms, Abhishek K. Sen, J. Andrew Jones
2 citations
Naturally occurring psychoactive compounds have been used for cultural and ethnomedical purposes for centuries. Several more such molecules continue to be chemically synthesized, exhibiting a wide range of potency, therapeutic, and hallucinogenic effects. Promising clinical data and a renewed interest in understanding the cellular mechanisms of action have inspired synthetic biology efforts to...
Metabolic Engineering
April 16, 2025
Madeleine R Keller, Madeline G. Mckinney, Abhishek K. Sen et al.
8 citations
Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is currently being studied in clinical trials as a treatment for severe mental health conditions, such as depression and anxiety. Previous reports of psilocybin biosynthesis as reconstituted in E. coli reported maximum titers of 1.16 g/L, exclusively using genes from the most common recreationally used mushroom,...
Biotechnology Progress
June 18, 2024
Xin Wang, Fiona C. Kanis, Caroline N. Broude et al.
2 citations
Abstract N ‐methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N ‐dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug...
British Journal of Pharmacology
June 2, 2024
Oscar Sandoval, Quynh Nguyen, Ryan J. Rakoczy et al.
23 citations
Background and Purpose Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing “magic” mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects....
Trends in biochemical sciences
March 1, 2024
Abhishek K. Sen, J. Andrew Jones
2 citations
A recent report by Chen et al. describes the discovery of RmNMT, a highly active and promiscuous tryptamine N-methyltransferase from the cane toad, Rhinella marina. N,N-dimethyltryptamine derivatives produced by this enzyme were then evaluated for their potential to serve as next-generation treatments for mental health disorders.
bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Ryan J. Rakoczy, Grace N. Runge, Abhishek K. Sen et al.
preprint
ABSTRACT Demand for more efficacious antidepressants, particularly those with a rapid onset of action, has resulted in a reevaluation of psychedelic drugs for their therapeutic potential. Several tryptamines found in psilocybin-containing ‘magic’ mushrooms share chemical similarities with psilocybin, and early work suggests they may also share receptor targets. However, few studies have...
Metabolic Engineering
May 23, 2023
Lucas M. Friedberg, Abhishek K. Sen, Quynh Nguyen et al.
22 citations
N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell...
Behavioural Brain Research
February 25, 2023
Brianna F Roberts, Alexia L Zylko, Courtney E Waters et al.
13 citations
Psilocybin and its active metabolite psilocin are hallucinogenic serotonergic agonists with high affinity for several serotonin receptors. In addition to underlying the hallucinogenic effects of these compounds, serotonin receptor activation also has important effects on decision-making and goal-directed behaviors. The impact of psilocybin and psilocin on these cognitive systems, however,...
Metabolic Engineering Communications
March 11, 2022
Alexandra M. Adams, Nicholas A. Anas, Abhishek K. Sen et al.
21 citations
Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. To date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, due to limitations around sourcing the phosphorylated tryptamine metabolite for in vivo testing. To address this limitation, we first developed a...