Design and fabrication of field-deployable microbial biosensing devices

Pham, Hoang Long; Ling, Hua

doi:10.1016/j.copbio.2022.102731

Cited by 8 publications

(3 citation statements)

References 49 publications

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“…The insight presented herethat the dynamics of burdensome genes in microbial communities can be stabilized via HGTis not limited to the case of engineering linear metabolic pathways. The stable persistence of many burdensome modules within engineered microbial systems could be used to implement many kinds of complex gene circuits, including those designed for multiplexed biosensing, biocomputing, microbiome engineering, and pattern formation. − …”

Section: Discussionmentioning

confidence: 99%

Programming Dynamic Division of Labor Using Horizontal Gene Transfer

Hamrick,

Maddamsetti,

Son

et al. 2024

ACS Synth. Biol.

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The metabolic engineering of microbes has broad applications, including biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multistep pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is the division of labor (DOL) in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted interstrain population dynamics. Through modeling, we show that dynamic division of labor (DDOL), which we define as the DOL between indiscrete populations capable of dynamic and reversible interchange, can overcome these limitations and enable the robust maintenance of burdensome, multistep pathways. We propose that DDOL can be mediated by horizontal gene transfer (HGT) and use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.

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Section: Discussionmentioning

confidence: 99%

Programming Dynamic Division of Labor Using Horizontal Gene Transfer

Hamrick,

Maddamsetti,

Son

et al. 2024

ACS Synth. Biol.

View full text Add to dashboard Cite

show abstract

“…The insight presented here-that the dynamics of burdensome genes in microbial communities can be stabilized via HGT-is not limited to the case of engineering linear metabolic pathways. The stable persistence of many burdensome modules within engineered microbial systems could be used to implement many kinds of complex gene circuits, including those designed for multiplexed biosensing, biocomputing, microbiome engineering, and pattern formation (60)(61)(62)(63)(64)(65).…”

Section: Discussionmentioning

confidence: 99%

Programming dynamic division of labor using horizontal gene transfer

Hamrick,

Maddamsetti,

Son

et al. 2023

Preprint

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The metabolic engineering of microbes has broad applications, including in biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multi-step pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is division of labor (DOL), in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted inter-strain population dynamics. Through modeling, we show that dynamic division of labor (DDOL) mediated by horizontal gene transfer (HGT) can overcome these limitations and enable the robust maintenance of burdensome, multi-step pathways. We also use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.

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“…In bacterial synthetic genetic circuits, genes work in orchestration to accomplish a variety of functions, from monitoring stress level and releasing drugs in the gut [1][2][3][4] , to sensing environmental pollutants in soil or water [5][6][7][8][9][10] . In these circuits, genes become dynamically activated and repressed, depending on the environment and on the circuit's state.…”

mentioning

confidence: 99%

Feedforward growth rate control mitigates gene activation burden

et al. 2022

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Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here, we introduce a feedforward controller that actuates growth rate upon activation of a gene of interest (GOI) to compensate for such a burden. The controller achieves this by activating a modified SpoT enzyme (SpoTH) with sole hydrolysis activity, which lowers ppGpp level and thus increases growth rate. An inducible RelA+ expression cassette further allows to precisely set the basal level of ppGpp, and thus nominal growth rate, in any bacterial strain. Without the controller, activation of the GOI decreased growth rate by more than 50%. With the controller, we could activate the GOI to the same level without growth rate defect. A cell strain armed with the controller in co-culture enabled persistent population-level activation of a GOI, which could not be achieved by a strain devoid of the controller. The feedforward controller is a tunable, modular, and portable tool that allows dynamic gene activation without growth rate defects for bacterial synthetic biology applications.

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Design and fabrication of field-deployable microbial biosensing devices

Cited by 8 publications

References 49 publications

Programming Dynamic Division of Labor Using Horizontal Gene Transfer

Programming Dynamic Division of Labor Using Horizontal Gene Transfer

Programming dynamic division of labor using horizontal gene transfer

Feedforward growth rate control mitigates gene activation burden

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