Engineering intelligent chassis cells via recombinase-based MEMORY circuits

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...

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Bibliographic Details
Published in:Nature communications 2024-03, Vol.15 (1), p.2418-2418, Article 2418
Main Authors: Huang, Brian D., Kim, Dowan, Yu, Yongjoon, Wilson, Corey J.
Format: Article
Language:English
Subjects:
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Arrays
Bacteroides thetaiotaomicron
Circuits
Computer memory
Decision making
Deoxyribonucleic acid
DNA
DNA - genetics
E coli
Engineers
Escherichia coli
Escherichia coli - genetics
Genetic diversity
Genetic programs
Genomics
Humanities and Social Sciences
Intelligence
Inversions
Memory cells
multidisciplinary
Probiotics
Recombinase
Recombinases - genetics
Science
Science (multidisciplinary)
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Summary: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 . The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-46755-1