A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes.
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.
DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.|BrisSynBio, University of Bristol , Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
Thomas E
TE
Gorochowski
Biochemistry, Institute of Biochemistry and Biology, University of Potsdam , 14476 Potsdam, Germany.
Irem
I
Avcilar-Kucukgoze
DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.|Synthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , 9747 AG Groningen, The Netherlands.
Roel A L
RA
Bovenberg
DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.
Johannes A
JA
Roubos
Biochemistry, Institute of Biochemistry and Biology, University of Potsdam , 14476 Potsdam, Germany.|Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg , 20146 Hamburg, Germany.
Zoya
Z
Ignatova
D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005813:Genes, Synthetic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D049452:Green Fluorescent Proteins
protein biosynthesis; synthetic biology; systems biology; translation