Design constraints in an operon circuit for engineered control of metabolic networks

D. A. Oyarzún; G. Stan

doi:10.1109/CDC.2012.6427048

Design constraints in an operon circuit for engineered control of metabolic networks

D. A. Oyarzún
, G. Stan

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

We consider a synthetic gene circuit aimed at regulating the flux through an unbranched metabolic network. The control circuit has an operon architecture whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We parameterize the gene regulatory model in terms of the promoter characteristic and ribosome binding site (RBS) strengths, both of which are common tuneable knobs in Synthetic Biology. We show that enzymatic saturation imposes bounds on the RBS strength design space. These bounds must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. Simulation results also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations.

Original language	English
Title of host publication	2012 IEEE 51st IEEE Conference on Decision and Control (CDC)
Pages	3608-3613
Number of pages	6
DOIs	https://doi.org/10.1109/CDC.2012.6427048
Publication status	Published - 1 Dec 2012
Event	51st IEEE Conference on Decision and Control (CDC) - Maui, United States Duration: 10 Dec 2012 → 13 Dec 2012 http://www.ieeecss.org/CAB/conferences/cdc2012/

Conference

Conference	51st IEEE Conference on Decision and Control (CDC)
Abbreviated title	CDC 2012
Country/Territory	United States
City	Maui
Period	10/12/12 → 13/12/12
Internet address	http://www.ieeecss.org/CAB/conferences/cdc2012/

Keywords / Materials (for Non-textual outputs)

biochemistry
biocontrol
compensation
enzymes
genetics
molecular biophysics
stability
operon circuit design constraints
engineered control
metabolic networks
synthetic gene circuit
flux regulation
unbranched metabolic network
control circuit
pathway enzymes
metabolic product
gene regulatory model
promoter characteristic
ribosome binding site strengths
synthetic biology
enzymatic saturation
RBS strength design space
metabolite accumulation
network stability
flux perturbation compensation
Biochemistry
Steady-state
Substrates
Integrated circuit modeling
Kinetic theory
Biological system modeling
Circuit stability

Access to Document

10.1109/CDC.2012.6427048

https://ieeexplore.ieee.org/document/6427048

Cite this

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title = "Design constraints in an operon circuit for engineered control of metabolic networks",

abstract = "We consider a synthetic gene circuit aimed at regulating the flux through an unbranched metabolic network. The control circuit has an operon architecture whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We parameterize the gene regulatory model in terms of the promoter characteristic and ribosome binding site (RBS) strengths, both of which are common tuneable knobs in Synthetic Biology. We show that enzymatic saturation imposes bounds on the RBS strength design space. These bounds must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. Simulation results also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations.",

keywords = "biochemistry, biocontrol, compensation, enzymes, genetics, molecular biophysics, stability, operon circuit design constraints, engineered control, metabolic networks, synthetic gene circuit, flux regulation, unbranched metabolic network, control circuit, pathway enzymes, metabolic product, gene regulatory model, promoter characteristic, ribosome binding site strengths, synthetic biology, enzymatic saturation, RBS strength design space, metabolite accumulation, network stability, flux perturbation compensation, Biochemistry, Steady-state, Substrates, Integrated circuit modeling, Kinetic theory, Biological system modeling, Circuit stability",

author = "Oyarz{\'u}n, \{D. A.\} and G. Stan",

year = "2012",

month = dec,

day = "1",

doi = "10.1109/CDC.2012.6427048",

language = "English",

pages = "3608--3613",

booktitle = "2012 IEEE 51st IEEE Conference on Decision and Control (CDC)",

note = "51st IEEE Conference on Decision and Control (CDC), CDC 2012 ; Conference date: 10-12-2012 Through 13-12-2012",

url = "http://www.ieeecss.org/CAB/conferences/cdc2012/",

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TY - GEN

T1 - Design constraints in an operon circuit for engineered control of metabolic networks

AU - Oyarzún, D. A.

AU - Stan, G.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - We consider a synthetic gene circuit aimed at regulating the flux through an unbranched metabolic network. The control circuit has an operon architecture whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We parameterize the gene regulatory model in terms of the promoter characteristic and ribosome binding site (RBS) strengths, both of which are common tuneable knobs in Synthetic Biology. We show that enzymatic saturation imposes bounds on the RBS strength design space. These bounds must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. Simulation results also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations.

AB - We consider a synthetic gene circuit aimed at regulating the flux through an unbranched metabolic network. The control circuit has an operon architecture whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We parameterize the gene regulatory model in terms of the promoter characteristic and ribosome binding site (RBS) strengths, both of which are common tuneable knobs in Synthetic Biology. We show that enzymatic saturation imposes bounds on the RBS strength design space. These bounds must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. Simulation results also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations.

KW - biochemistry

KW - biocontrol

KW - compensation

KW - enzymes

KW - genetics

KW - molecular biophysics

KW - stability

KW - operon circuit design constraints

KW - engineered control

KW - metabolic networks

KW - synthetic gene circuit

KW - flux regulation

KW - unbranched metabolic network

KW - control circuit

KW - pathway enzymes

KW - metabolic product

KW - gene regulatory model

KW - promoter characteristic

KW - ribosome binding site strengths

KW - synthetic biology

KW - enzymatic saturation

KW - RBS strength design space

KW - metabolite accumulation

KW - network stability

KW - flux perturbation compensation

KW - Biochemistry

KW - Steady-state

KW - Substrates

KW - Integrated circuit modeling

KW - Kinetic theory

KW - Biological system modeling

KW - Circuit stability

U2 - 10.1109/CDC.2012.6427048

DO - 10.1109/CDC.2012.6427048

M3 - Conference contribution

SP - 3608

EP - 3613

BT - 2012 IEEE 51st IEEE Conference on Decision and Control (CDC)

T2 - 51st IEEE Conference on Decision and Control (CDC)

Y2 - 10 December 2012 through 13 December 2012

ER -

Design constraints in an operon circuit for engineered control of metabolic networks

Abstract

Conference

Keywords / Materials (for Non-textual outputs)

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Cite this