Two cellular resource‐based models linking growth and parts characteristics aids the study and optimisation of synthetic gene circuits. Issue 1 (10th May 2017)

• Record Type: Journal Article
• Authors: Wang, Huijuan; Ling, Maurice H.T.; Chua, Tze Kwang; Poh, Chueh Loo
• Is Part Of: Engineering biology. Volume 1:Issue 1(2017)
• Page Start: 30
• Page End: 39
• Publication Date: 2017-05-10
• Subjects: cellular biophysics -- genetics -- microorganisms -- molecular biophysics -- physiological models -- proteins; Escherichia coli growth rate -- ribosome binding site -- biophysical models -- heterologous protein abundance -- heterologous gene expressions -- synthetic gene circuit optimisation -- cellular resource‐based models; Bioengineering -- Periodicals; Bioengineering; Periodicals; 660.605
• DOI: 10.1049/enb.2017.0005
• Languages: English
• ISSNs: 2398-6182

Abstract

Abstract : 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).