Engineered bacterial prodrug-activating enzyme

Engineered bacterial prodrug-activating enzymes are a class of non-human enzymes, such as cytosine deaminase (CD) or nitroreductase (NTR), that have been genetically modified to optimize their catalytic efficiency, substrate specificity, or stability for therapeutic use (Sharrock et al., 2022). These enzymes are typically delivered to the tumor microenvironment using engineered bacterial vectors, such as attenuated strains of Salmonella typhimurium or Escherichia coli, in a strategy known as Bacteria-Directed Enzyme Prodrug Therapy (BDEPT) (NIH, 2021). The bacteria selectively colonize the hypoxic and necrotic regions of solid tumors, where they express the enzyme to serve as a localized drug factory (BioRxiv, 2026). Upon systemic administration of a non-toxic prodrug, such as 5-fluorocytosine or CB1954, the enzyme catalyzes its conversion into a highly potent cytotoxic agent like 5-fluorouracil or a DNA-alkylating mustard (Zhao et al., 2023). This localized activation allows for high concentrations of the active drug within the tumor while significantly reducing systemic exposure and associated side effects (NIH, 2023). This approach is primarily investigated for the treatment of refractory solid tumors, leveraging the unique tumor-homing capabilities of certain bacteria to overcome the limitations of conventional chemotherapy (Preprints.org, 2025).

Other names

Prodrug-converting enzymeBDEPT enzymeBacterial prodrug-activating enzymeExogenous prodrug-activating enzymeGDEPT enzyme

The target functions as a localized metabolic catalyst that converts an inert, systemically administered prodrug into a potent cytotoxic metabolite within the tumor microenvironment (NIH, 2023). This is achieved by delivering the enzyme gene or protein via engineered bacterial vectors that selectively colonize and proliferate in the unique conditions of the tumor (BioRxiv, 2026).