Unleashing Synthetic Biology to Cure TMAU

Trimethylamine (TMA) is a volatile tertiary aliphatic amine primarily derived from dietary consumption. In the human body, this compound typically undergoes metabolism by the enzyme flavin-containing monooxygenase 3 (FMO3) into a less malodorous byproduct - trimethylamine N-oxide (TMAO). 

While microbiome often assist those with less efficient digestive genes to metabolize food, as observed in cases of lactose intolerance, FMO3 enzyme is an exception as it is not naturally produced by bacteria, only in humans, primates and some mammals.

Fortunately, a similar enzyme, Trimethylamine monooxygenase (TMM), can catalyze the oxidation of TMA to TMAO. Notably, this enzyme is found in the marine bacterium Ruegeria pomeroyi.

Building on the groundbreaking efforts of a preceding team that successfully synthesized TMM from Ruegeria pomeroyi and expressed it in E. coli, this year's Florida State University (FSU) iGEM team is poised to expand this research further. Leveraging promoters crafted by previous FSU iGEM teams (from 2018 and 2020) and armed with a FMO3 CRISPR/Cas9 Plasmid, they are geared up to take the reins and explore new frontiers in the treatment of TMAU using synthetic biology.

With the initiation of this year's competition, the FSU team is now racing against time. With two months to see their project to completion, they're equipped with three plasmids, a wealth of knowledge, and a strong determination to discover a therapy for TMAU, a metabolic disorder that has no cure.

The process won't be easy. The late nights in the lab, the countless trials and failures, and the endless tweaking of protocols are all part of this journey. But the prospect of developing a therapy for TMAU and pushing the boundaries of synthetic biology, make the journey worth every challenge.

Today we learned about some of the details of the project from Human Practices leads Christian Suastegui and Colton Keib. Other student members of the team are Graeme Pugsley, Eva Lobaton, John Amos, Jolene Jones, Hanna Yilmaz-Rodriguez, Sonali Shakya, Vicenzo DeVito and Prerna Ravinder.  The team lead is Elizabeth Moore. Read FSU blog and our updates and stay tuned as we follow this team's exciting adventure. 

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