Anxiety is one of the most widespread mental illnesses of the 21st century, affecting hundreds of millions of individuals around the globe. Anxiety is characterized by excessive and intrusive worry, fear, and physical symptoms such as rapid heart, sweating, and tension. While anxiety is a normal response to stress, anxiety disorders occur when these responses are persistent, disproportionate, and interfere with functioning. Anxiety disorders are the leading mental health disorders worldwide, according to the World Health Organization (WHO), with an estimated 301 million people affected in 2019 alone—a number that has only increased with international stressors like pandemics, climate crises, and economic downturn. Anxiety is specifically prevalent in adolescents and young adults, impacting academic achievement, social relationships, and overall well-being.

Current treatment options are cognitive behavioral therapy (CBT), medication such as selective serotonin reuptake inhibitors (SSRIs), and lifestyle change. These treatments are not effective in all patients and are always associated with side effects, tardive response, or unavailability based on affordability and availability of mental health professionals. The biological underpinnings of anxiety are complex and involve an interaction between neurotransmitters, hormones, and genetic factors. Further, recent evidence has also begun to elucidate the mechanism of action of the gut-brain axis, microbiome, and neuroinflammation on mood and anxiety-related behaviors. In iGEM 2025, our team will seek new, biology-based solutions for the treatment of anxiety by employing synthetic biology to investigate and potentially engineer the underlying molecular pathways. Through the convergence of advances in biotechnology with the urgent need for a global health burden, we seek to enable more precise, cost-effective, and potent treatments for people afflicted by anxiety.

Our idea was based on trying to solve the main problem of anxiety and its huge effect on students, inspired from our everyday life. We chose linalool and nerolidol, since they are valuable terpenoids with applications in fragrances, flavors, and potentially as bio-based alternatives to synthetic chemicals. However, their natural extraction from plants is inefficient and costly. So we had to ask ourselves how we could engineer a microbial system to produce these compounds more sustainably? We chose yeast (S. cerevisiae) because it is a well-established host for metabolic engineering of terpenoids and already has the mevalonate pathway that can be redirected toward linalool and nerolidol synthesis.

We decided to use an Addgene plasmid carrying the necessary genes, because this gave us a reliable and accessible genetic tool without needing to design everything from scratch. To recover the products, we adapted the olive oil overlay method for in situ extraction, since terpenoids are hydrophobic and can be lost through evaporation. Finally, we added fractional distillation to purify the products from other alcohols, ensuring we could test both yield and specificity. Our idea is a result of the combination of the challenge of sustainable terpenoid production, the strengths of yeast as a chassis, and the existing protocols for plasmid prep, transformation, fermentation, and extraction into one integrated workflow. This is how Mavericks will try to help students’ anxiety, through the metabolic engineering of saccharomyces cerevisiae for the biosynthesis of linalool, as an extracted purified oil with therapeutic effects.