Genetic Circuits for Feedback Control of Gamma-Aminobutyric Acid Biosynthesis in Probiotic Escherichia coli Nissle 1917

Authors

Matthew Lebovich, University of Massachusetts AmherstFollow
Marcos A. Lora, University of Massachusetts AmherstFollow
Jared Gracia-David, Amherst CollegeFollow
Lauren Andrews, University of Massachusetts AmherstFollow

Publication Date

2024

Journal or Book Title

Metabolites

Abstract

Engineered microorganisms such as the probiotic strain Escherichia coli Nissle 1917 (EcN) offer a strategy to sense and modulate the concentration of metabolites or therapeutics in the gastrointestinal tract. Here, we present an approach to regulate the production of the depression-associated metabolite gamma-aminobutyric acid (GABA) in EcN using genetic circuits that implement negative feedback. We engineered EcN to produce GABA by overexpressing glutamate decarboxylase and applied an intracellular GABA biosensor to identify growth conditions that improve GABA biosynthesis. We next employed characterized genetically encoded NOT gates to construct genetic circuits with layered feedback to control the rate of GABA biosynthesis and the concentration of GABA produced. Looking ahead, this approach may be utilized to design feedback control of microbial metabolite biosynthesis to achieve designable smart microbes that act as living therapeutics.

ORCID

Andrews: https://orcid.org/0000-0003-1627-1430

DOI

https://doi.org/10.3390/metabo14010044

Pages

44

Volume

14

Issue

1

License

UMass Amherst Open Access Policy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Funder

NSF CBET-1943695, NSF MCB-2211039, NIH T32 GM135096

Recommended Citation

Lebovich, Matthew; Lora, Marcos A.; Gracia-David, Jared; and Andrews, Lauren, "Genetic Circuits for Feedback Control of Gamma-Aminobutyric Acid Biosynthesis in Probiotic Escherichia coli Nissle 1917" (2024). Metabolites. 929.
https://doi.org/10.3390/metabo14010044