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

ABSTRACT: 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 acc

SUBMITTER: Chen J 

PROVIDER: S-EPMC8449674 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature