Biosensor-based growth-coupling and spatial separation as an evolution strategy to improve small molecule production of Corynebacterium glutamicum.
Metab Eng
; 68: 162-173, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34628038
ABSTRACT
Evolutionary engineering is a powerful method to improve the performance of microbial cell factories, but can typically not be applied to enhance the production of chemicals due to the lack of an appropriate selection regime. We report here on a new strategy based on transcription factor-based biosensors, which directly couple production to growth. The growth of Corynebacterium glutamicum was coupled to the intracellular concentration of branched-chain amino acids, by integrating a synthetic circuit based on the Lrp biosensor upstream of two growth-regulating genes, pfkA and hisD. Modelling and experimental data highlight spatial separation as key strategy to limit the selection of 'cheater' strains that escaped the evolutionary pressure. This approach facilitated the isolation of strains featuring specific causal mutations enhancing amino acid production. We envision that this strategy can be applied with the plethora of known biosensors in various microbes, unlocking evolution as a feasible strategy to improve production of chemicals.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biosensing Techniques
/
Corynebacterium glutamicum
Type of study:
Prognostic_studies
Language:
En
Journal:
Metab Eng
Journal subject:
ENGENHARIA BIOMEDICA
/
METABOLISMO
Year:
2021
Document type:
Article
Affiliation country:
Germany