Engineering intelligent chassis cells via recombinase-based MEMORY circuits

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 co...

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Main Authors: Brian D. Huang, Dowan Kim, Yongjoon Yu, Corey J. Wilson
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46755-1
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author Brian D. Huang
Dowan Kim
Yongjoon Yu
Corey J. Wilson
author_facet Brian D. Huang
Dowan Kim
Yongjoon Yu
Corey J. Wilson
author_sort Brian D. Huang
collection DOAJ
description 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.
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spelling doaj.art-32f676996b1c4a7d9964cfa5c4d5e3942024-03-24T12:25:26ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46755-1Engineering intelligent chassis cells via recombinase-based MEMORY circuitsBrian D. Huang0Dowan Kim1Yongjoon Yu2Corey J. Wilson3Georgia Institute of Technology, School of Chemical & Biomolecular EngineeringGeorgia Institute of Technology, School of Chemical & Biomolecular EngineeringGeorgia Institute of Technology, School of Chemical & Biomolecular EngineeringGeorgia Institute of Technology, School of Chemical & Biomolecular EngineeringAbstract 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.https://doi.org/10.1038/s41467-024-46755-1
spellingShingle Brian D. Huang
Dowan Kim
Yongjoon Yu
Corey J. Wilson
Engineering intelligent chassis cells via recombinase-based MEMORY circuits
Nature Communications
title Engineering intelligent chassis cells via recombinase-based MEMORY circuits
title_full Engineering intelligent chassis cells via recombinase-based MEMORY circuits
title_fullStr Engineering intelligent chassis cells via recombinase-based MEMORY circuits
title_full_unstemmed Engineering intelligent chassis cells via recombinase-based MEMORY circuits
title_short Engineering intelligent chassis cells via recombinase-based MEMORY circuits
title_sort engineering intelligent chassis cells via recombinase based memory circuits
url https://doi.org/10.1038/s41467-024-46755-1
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AT coreyjwilson engineeringintelligentchassiscellsviarecombinasebasedmemorycircuits