Engineering intelligent chassis cells via recombinase-based MEMORY circuits

Brian D. Huang, Dowan Kim, Yongjoon Yu and Corey J. Wilson ()
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Brian D. Huang: School of Chemical & Biomolecular Engineering
Dowan Kim: School of Chemical & Biomolecular Engineering
Yongjoon Yu: School of Chemical & Biomolecular Engineering
Corey J. Wilson: School of Chemical & Biomolecular Engineering

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Synthetic biologists seek to engineer intelligent living systems capable of decision-making, communication, and memory. Separate technologies exist for each tenet of intelligence; however, the unification of all three properties in a living system has not been achieved. Here, we engineer completely intelligent Escherichia coli strains that harbor six orthogonal and inducible genome-integrated recombinases, forming Molecularly Encoded Memory via an Orthogonal Recombinase arraY (MEMORY). MEMORY chassis cells facilitate intelligence via the discrete multi-input regulation of recombinase functions enabling inheritable DNA inversions, deletions, and genomic insertions. MEMORY cells can achieve programmable and permanent gain (or loss) of functions extrachromosomally or from a specific genomic locus, without the loss or modification of the MEMORY platform – enabling the sequential programming and reprogramming of DNA circuits within the cell. We demonstrate all three tenets of intelligence via a probiotic (Nissle 1917) MEMORY strain capable of information exchange with the gastrointestinal commensal Bacteroides thetaiotaomicron.

Date: 2024
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DOI: 10.1038/s41467-024-46755-1

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