Engineering a probiotic strain of Escherichia coli to induce the regression of colorectal cancer through production of 5-aminolevulinic acid.

Bacterial vectors can be engineered to generate microscopic living therapeutics to produce and deliver anticancer agents. Escherichia coli Nissle 1917 (Nissle 1917) is a promising candidate with probiotic properties. Here, we used Nissle 1917 to develop a metabolic strategy to produce 5‐aminolevulinic acid (5‐ALA) from glucose as 5‐ALA plays an important role in the photodynamic therapy of cancers. The coexpression of hemA M and hemL using a low copy‐number plasmid led to remarkable accumulation of 5‐ALA. The downstream pathway of 5‐ALA biosynthesis was inhibited by levulinic acid (LA). Small‐scale cultures of engineered Nissle 1917 produced 300 mg l−1 of 5‐ALA. Recombinant Nissle 1917 was applied to deliver 5‐ALA to colorectal cancer cells, in which it induced the accumulation of antineoplastic protoporphyrin X (PpIX) and specific cytotoxicity towards colorectal cancer cells irradiated with a 630 nm laser. Moreover, this novel combination therapy proved effective in a mouse xenograft model and was not cytotoxic to normal tissues. These findings suggest that Nissle 1917 will serve as a potential carrier to effectively deliver 5‐ALA for cancer therapy.