BIOSYNTHESIS OF ENZYMES FOR USE IN TREATMENT OF MAPLE SYRUP URINE DISEASE (MSUD)

The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patients internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells comprising a heterologous gene encoding an improved leucine catabolism enzyme with higher activity and/or specificity for leucine over other branched chain amino acids, such as isoleucine or valine. The disclosure further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders involving the catabolism of leucine, isoleucine, and/or valine using the pharmaceutical compositions disclosed herein.