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access icon openaccess Two cellular resource-based models linking growth and parts characteristics aids the study and optimisation of synthetic gene circuits

This is an open access article published by the IET under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/)
Received 27/02/2017, Accepted 27/03/2017, Published 10/05/2017

A major challenge in synthetic genetic circuit development is the inter-dependency between heterologous gene expressions by circuits and host's growth rate. Increasing heterologous gene expression increases burden to the host, resulting in host growth reduction; which reduces overall heterologous protein abundance. Hence, it is difficult to design predictable genetic circuits. Here, we develop two biophysical models; one for promoter, another for RBS; to correlate heterologous gene expression and growth reduction. We model cellular resource allocation in E. coli to describe the burden, as growth reduction, caused by genetic circuits. To facilitate their uses in genetic circuit design, inputs to the model are common characteristics of biological parts [e.g. relative promoter strength (RPU) and relative ribosome binding sites strength (RRU)]. The models suggest that E. coli's growth rate reduces linearly with increasing RPU/RRU of the genetic circuits; thus, providing 2 handy models taking parts characteristics as input to estimate growth rate reduction for fine tuning genetic circuit design in silico prior to construction. Our promoter model correlates well with experiments using various genetic circuits, both single and double expression cassettes, up to a relative promoter unit of 3.7 with a 60% growth rate reduction (average R 2∼0.9).

Inspec keywords: physiological models; genetics; cellular biophysics; molecular biophysics; microorganisms; proteins

Other keywords: synthetic gene circuit optimisation; ribosome binding site; biophysical models; Escherichia coli growth rate; cellular resource-based models; heterologous protein abundance; heterologous gene expressions

Subjects: Biomolecular interactions, charge transfer complexes; Physics of subcellular structures

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http://iet.metastore.ingenta.com/content/journals/10.1049/enb.2017.0005
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