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

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TitleBacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition.
Publication TypeJournal Article
Year of Publication2019
AuthorsStephens, K, Pozo, M, Tsao, C-Y, Hauk, P, Bentley, WE
JournalNat Commun
Volume10
Issue1
Pagination4129
Date Published2019 Sep 11
ISSN2041-1723
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.

DOI10.1038/s41467-019-12027-6
Alternate JournalNat Commun
PubMed ID31511505
PubMed Central IDPMC6739400