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ACS Synth Biol. 2016 Jul 15;5(7):710-20. doi: 10.1021/acssynbio.6b00040. Epub 2016 May 3.

A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes.

Author information

1
DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.
2
BrisSynBio, University of Bristol , Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
3
Biochemistry, Institute of Biochemistry and Biology, University of Potsdam , 14476 Potsdam, Germany.
4
Synthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , 9747 AG Groningen, The Netherlands.
5
Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg , 20146 Hamburg, Germany.

Abstract

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.

KEYWORDS:

protein biosynthesis; synthetic biology; systems biology; translation

PMID:
27112032
DOI:
10.1021/acssynbio.6b00040
[Indexed for MEDLINE]
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