Enhancing circuit stability under growth feedback with supplementary repressive regulation.
Nucleic Acids Res
; 52(3): 1512-1521, 2024 Feb 09.
Article
en En
| MEDLINE
| ID: mdl-38164993
ABSTRACT
The field of synthetic biology and biosystems engineering increasingly acknowledges the need for a holistic design approach that incorporates circuit-host interactions into the design process. Engineered circuits are not isolated entities but inherently entwined with the dynamic host environment. One such circuit-host interaction, 'growth feedback', results when modifications in host growth patterns influence the operation of gene circuits. The growth-mediated effects can range from growth-dependent elevation in protein/mRNA dilution rate to changes in resource reallocation within the cell, which can lead to complete functional collapse in complex circuits. To achieve robust circuit performance, synthetic biologists employ a variety of control mechanisms to stabilize and insulate circuit behavior against growth changes. Here we propose a simple strategy by incorporating one repressive edge in a growth-sensitive bistable circuit. Through both simulation and in vitro experimentation, we demonstrate how this additional repressive node stabilizes protein levels and increases the robustness of a bistable circuit in response to growth feedback. We propose the incorporation of repressive links in gene circuits as a control strategy for desensitizing gene circuits against growth fluctuations.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Redes Reguladoras de Genes
/
Biología Sintética
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2024
Tipo del documento:
Article