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Redesign of an Escherichia coli Nissle treatment for phenylketonuria using insulated genomic landing pads and genetic circuits to reduce burden

ABSTRACT: To build therapeutic strains, Escherichia coli Nissle (EcN) have been engineered to express antibiotics, toxin-degrading enzymes, immunoregulators, and anti-cancer chemotherapies. For efficacy, the recombinant genes need to be highly expressed, but this imposes a burden on the cell, and plasmids are difficult to maintain in the body. To address these problems, we have developed landing pads in the EcN genome and genetic circuits to control therapeutic gene expression. These tools were applied to EcN SYNB1618, undergoing clinical trials as a phenylketonuria treatment. The pathway for converting phenylalanine to trans-cinnamic acid was moved to a landing pad under the control of a circuit that keeps the pathway off during storage. The resulting strain (EcN SYN8784) achieved higher activity than EcN SYNB1618, reaching levels near when the pathway is carried on a plasmid. This work demonstrates a simple system for engineering EcN that aids quantitative strain design for therapeutics.

ORGANISM(S): Escherichia coli Nissle 1917

PROVIDER: GSE228761 | GEO | 2023/05/15

REPOSITORIES: GEO

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E. coli Nissle 1917 transcriptional response after treatment with Calprotectin

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Proteomic analysis of outer membrane vesicles from the probiotic strain Escherichia coli Nissle 1917

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2013-12-19 | PXD000367 | Pride

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The probiotic Escherichia coli strain Nissle 1917 combats the lambdoid bacteriophages stx and λ

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RNA-Seq of Escherichia coli Nissle 1917 strains modified to produce different amounts of the bacteriocin microcin C

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2023-06-30 | E-MTAB-13078 | biostudies-arrayexpress

K5 capsule and lipopolysaccharide are important in resistance to T4 phage attack in probiotic E. coli strain Nissle 1917

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Recombinant Production of Biliverdin IXβ and δ Isomers in the T7 Promoter Compatible Escherichia coli Nissle

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2005-03-02 | GSE2232 | GEO

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