The interrelationship between promoter strength, gene expression, and growth rate

Matthew S. Bienick, Katherine W. Young, Justin R. Klesmith, Emily E. Detwiler, Kyle J. Tomek, Timothy A. Whitehead

    Research output: Research - peer-reviewArticle

    • 16 Citations

    Abstract

    In exponentially growing bacteria, expression of heterologous protein impedes cellular growth rates. Quantitative understanding of the relationship between expression and growth rate will advance our ability to forward engineer bacteria, important for metabolic engineering and synthetic biology applications. Recently, a work described a scaling model based on optimal allocation of ribosomes for protein translation. This model quantitatively predicts a linear relationship between microbial growth rate and heterologous protein expression with no free parameters. With the aim of validating this model, we have rigorously quantified the fitness cost of gene expression by using a library of synthetic constitutive promoters to drive expression of two separate proteins (eGFP and amiE) in E. coli in different strains and growth media. In all cases, we demonstrate that the fitness cost is consistent with the previous findings. We expand upon the previous theory by introducing a simple promoter activity model to quantitatively predict how basal promoter strength relates to growth rate and protein expression. We then estimate the amount of protein expression needed to support high flux through a heterologous metabolic pathway and predict the sizable fitness cost associated with enzyme production. This work has broad implications across applied biological sciences because it allows for prediction of the interplay between promoter strength, protein expression, and the resulting cost to microbial growth rates.

    LanguageEnglish (US)
    Article numbere109105
    JournalPLoS One
    Volume9
    Issue number10
    DOIs
    StatePublished - Oct 6 2014

    Profile

    promoter regions
    gene expression
    Gene Expression
    Growth
    Proteins
    Gene expression
    protein synthesis
    Costs and Cost Analysis
    Costs
    microbial growth
    bacteria
    proteins
    heterologous gene expression
    Bacteria
    synthetic biology
    metabolic engineering
    ribosomes
    engineers
    translation (genetics)
    biochemical pathways

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Bienick, M. S., Young, K. W., Klesmith, J. R., Detwiler, E. E., Tomek, K. J., & Whitehead, T. A. (2014). The interrelationship between promoter strength, gene expression, and growth rate. PLoS One, 9(10), [e109105]. DOI: 10.1371/journal.pone.0109105

    The interrelationship between promoter strength, gene expression, and growth rate. / Bienick, Matthew S.; Young, Katherine W.; Klesmith, Justin R.; Detwiler, Emily E.; Tomek, Kyle J.; Whitehead, Timothy A.

    In: PLoS One, Vol. 9, No. 10, e109105, 06.10.2014.

    Research output: Research - peer-reviewArticle

    Bienick, MS, Young, KW, Klesmith, JR, Detwiler, EE, Tomek, KJ & Whitehead, TA 2014, 'The interrelationship between promoter strength, gene expression, and growth rate' PLoS One, vol 9, no. 10, e109105. DOI: 10.1371/journal.pone.0109105
    Bienick MS, Young KW, Klesmith JR, Detwiler EE, Tomek KJ, Whitehead TA. The interrelationship between promoter strength, gene expression, and growth rate. PLoS One. 2014 Oct 6;9(10). e109105. Available from, DOI: 10.1371/journal.pone.0109105
    Bienick, Matthew S. ; Young, Katherine W. ; Klesmith, Justin R. ; Detwiler, Emily E. ; Tomek, Kyle J. ; Whitehead, Timothy A./ The interrelationship between promoter strength, gene expression, and growth rate. In: PLoS One. 2014 ; Vol. 9, No. 10.
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