IPRD funded research by Cesar Rodriguez
Fish odor syndrome or trimethylaminuria (TMAU) is a condition where patients have an odor of rotting fish due to the presence of trimethylamine (TMA) in their urine, sweat, and breath. The global prevalence of TMAU is estimated at 1 in 200,000 to 1 in 1,000,000 but due to lack of awareness and low diagnosis rates, the true prevalence may be higher. TMAU can present at any age, although symptoms often become more noticeable during puberty. Patients with TMAU experience social isolation, anxiety, and high rates of depression. No cure exists and the condition is managed with dietary modification, antibiotic therapy, activated charcoal administration, modifications to personal hygiene, and psychological support. Gut microflora normally convert certain amino acids into TMA in the small and large intestines. TMA is then converted to trimethylamine-N-oxide (TMAO) in the liver by the enzyme flavin-containing monooxygenase 3 (FMO3). TMAO is odorless. TMAU patients have a genetic mutation that produces dysfunctional or low levels of FMO3 resulting in the accumulation, secretion, and emission of TMA. This research project will design, build, and test three FDA-approved strains of engineered E. coli that can convert TMA to TMAO in the small and large intestines, as a candidate cell-based therapeutic for TMAU.
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