Dynamic cybergenetic control of bacterial co-culture composition via optogenetic feedback

Joaquín Gutiérrez Mena, Sant Kumar and Mustafa Khammash ()
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Joaquín Gutiérrez Mena: Department of Biosystems Science and Engineering (D-BSSE), ETH Zürich
Sant Kumar: Department of Biosystems Science and Engineering (D-BSSE), ETH Zürich
Mustafa Khammash: Department of Biosystems Science and Engineering (D-BSSE), ETH Zürich

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Communities of microbes play important roles in natural environments and hold great potential for deploying division-of-labor strategies in synthetic biology and bioproduction. However, the difficulty of controlling the composition of microbial consortia over time hinders their optimal use in many applications. Here, we present a fully automated, high-throughput platform that combines real-time measurements and computer-controlled optogenetic modulation of bacterial growth to implement precise and robust compositional control of a two-strain E. coli community. In addition, we develop a general framework for dynamic modeling of synthetic genetic circuits in the physiological context of E. coli and use a host-aware model to determine the optimal control parameters of our closed-loop compositional control system. Our platform succeeds in stabilizing the strain ratio of multiple parallel co-cultures at arbitrary levels and in changing these targets over time, opening the door for the implementation of dynamic compositional programs in synthetic bacterial communities.

Date: 2022
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DOI: 10.1038/s41467-022-32392-z

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