Programming Probiotics: Diet-Responsive Gene Expression and Colonization Control in Engineered S. boulardii.
ACS Synth Biol
; 13(6): 1851-1865, 2024 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38787439
ABSTRACT
Saccharomyces boulardii (Sb) is an emerging probiotic chassis for delivering biomolecules to the mammalian gut, offering unique advantages as the only eukaryotic probiotic. However, precise control over gene expression and gut residence time in Sb have remained challenging. To address this, we developed five ligand-responsive gene expression systems and repaired galactose metabolism in Sb, enabling inducible gene expression in this strain. Engineering these systems allowed us to construct AND logic gates, control the surface display of proteins, and turn on protein production in the mouse gut in response to dietary sugar. Additionally, repairing galactose metabolism expanded Sb's habitat within the intestines and resulted in galactose-responsive control over gut residence time. This work opens new avenues for precise dosing of therapeutics by Sb via control over its in vivo gene expression levels and localization within the gastrointestinal tract.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Probiotics
/
Saccharomyces boulardii
/
Galactose
Limits:
Animals
Language:
En
Journal:
ACS Synth Biol
Year:
2024
Type:
Article
Affiliation country:
United States