Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition

Kristina Stephens, Maria Pozo, Chen-Yu Tsao, Pricila Hauk and William E. Bentley ()
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Kristina Stephens: University of Maryland
Maria Pozo: University of Maryland
Chen-Yu Tsao: University of Maryland
Pricila Hauk: University of Maryland
William E. Bentley: University of Maryland

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Synthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic and regulatory components can, however, overburden the reprogrammed cells. In order to avoid metabolic overload, an emerging area of focus is on engineering consortia, wherein cell subpopulations work together to carry out a desired function. This strategy requires regulation of the cell populations. Here, we design a synthetic co-culture controller consisting of cell-based signal translator and growth-controller modules that, when implemented, provide for autonomous regulation of the consortia composition. The system co-opts the orthogonal autoinducer AI-1 and AI-2 cell-cell signaling mechanisms of bacterial quorum sensing (QS) to enable cross-talk between strains and a QS signal-controlled growth rate controller to modulate relative population densities. We further develop a simple mathematical model that enables cell and system design for autonomous closed-loop control of population trajectories.

Date: 2019
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DOI: 10.1038/s41467-019-12027-6

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