Metabolic engineering of probiotic Escherichia coli for cytolytic therapy of tumors.

ABSTRACT: Bacterial cancer therapy was developed using probiotic Escherichia coli Nissle 1917 (EcN) for medical intervention of colorectal cancer. EcN was armed with HlyE, a small cytotoxic protein, under the control of the araBAD promoter (P_BAD). The intrinsic limitation of P_BAD for the gene expression is known to be negated by glucose and afflicted with all-or-nothing induction in host bacteria. This issue was addressed by metabolic engineering of EcN to uncouple the glucose-mediated control circuit and the L-arabinose transport-induction loop and to block L-arabinose catabolism. As a result, the reprogrammed strain (designated EcNe) enabled efficient expression of HlyE in a temporal control manner. The HlyE production was insensitive to glucose and reached a saturated level

SUBMITTER: Chiang CJ 

PROVIDER: S-EPMC7971005 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature