TY  - JOUR
A1  - Gorochowski, Thomas E.
A1  - Aycilar-Kucukgoze, Irem
A1  - Bovenberg, Roel A. L.
A1  - Roubos, Johannes A.
A1  - Ignatova, Zoya
T1  - A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes
JF  - ACS synthetic biology
N2  - Cells contain a finite set of resources that must be distributed across many processes to ensure survival. Among them, the largest proportion of cellular resources is dedicated to protein translation. Synthetic biology often exploits these resources in executing orthogonal genetic circuits, yet the burden this places on the cell is rarely considered. Here, we develop a minimal model of ribosome allocation dynamics capturing the demands on translation when expressing a synthetic construct together with endogenous genes required for the maintenance of cell physiology. Critically, it contains three key variables related to design parameters of the synthetic construct covering transcript abundance, translation initiation rate, and elongation time. We show that model-predicted changes in ribosome allocation closely match experimental shifts in synthetic protein expression rate and cellular growth. Intriguingly, the model is also able to accurately infer transcript levels and translation times after further exposure to additional ambient stress. Our results demonstrate that a simple model of resource allocation faithfully captures the redistribution of protein synthesis resources when faced with the burden of synthetic gene expression and environmental stress. The tractable nature of the model makes it a versatile tool for exploring the guiding principles of efficient heterologous expression and the indirect interactions that can arise between synthetic circuits and their host chassis because of competition for shared translational resources.
KW  - protein biosynthesis
KW  - translation
KW  - synthetic biology
KW  - systems biology
Y1  - 2016
U6  - https://doi.org/10.1021/acssynbio.6b00040
SN  - 2161-5063
VL  - 5
SP  - 710
EP  - 720
PB  - American Chemical Society
CY  - Washington
ER  -