Synthesis of versatile neuromodulatory molecules by a gut microbial glutamate decarboxylase

Dysbiosis of the microbiome correlates with many neurological disorders, yet very little is known about the chemistry that controls the production of neuromodulatory molecules by gut microbes. Here, we found that an enzyme glutamate decarboxylase (BfGAD) of a gut microbe Bacteroides fragilis forms multiple neuromodulatory molecules such as γ-aminobutyric acid (GABA), hypotaurine, taurine, homotaurine, and β-alanine. We evolved BfGAD and doubled its taurine productivity. Additionally, we increased its specificity toward the substrate L-glutamate. Here, we provide a chemical strategy via which the BfGAD activity could be fine-tuned. In future, this strategy could be used to modulate the production of neuromodulatory molecules by gut microbes.