Design tradeoffs in a synthetic gene control circuit for metabolic networks

D. A. Oyarzún; G. Stan

doi:10.1109/ACC.2012.6314705

Design tradeoffs in a synthetic gene control circuit for metabolic networks

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

Abstract

The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.

Original language	English
Title of host publication	2012 American Control Conference (ACC)
Pages	2743-2748
Number of pages	6
DOIs	https://doi.org/10.1109/ACC.2012.6314705
Publication status	Published - 1 Jun 2012
Event	2012 American Control Conference, ACC 2012 - Montreal, QC, Canada Duration: 27 Jun 2012 → 29 Jun 2012

Conference

Conference	2012 American Control Conference, ACC 2012
Country/Territory	Canada
City	Montreal, QC
Period	27/06/12 → 29/06/12

Keywords / Materials (for Non-textual outputs)

biochemistry
biocontrol
biotechnology
cellular biophysics
enzymes
topology
transient response
design tradeoffs
synthetic gene control circuit
metabolic networks
metabolism
metabolic steady state
regulatory topology
design parameters
transcriptional control circuit
unbranched metabolic pathway
saturable enzyme kinetics
nonoperon topologies
operon topologies
enzyme half-lives
changing metabolic demand
basal enzyme expression
regulatory sensitivity
steady state product bias
Biochemistry
Steady-state
Mathematical model
Genetics
Kinetic theory
Jacobian matrices
Eigenvalues and eigenfunctions

Access to Document

10.1109/ACC.2012.6314705

https://ieeexplore.ieee.org/document/6314705

Cite this

@inproceedings{282a834ca460420f8963a40fc2447b6b,

title = "Design tradeoffs in a synthetic gene control circuit for metabolic networks",

abstract = "The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.",

keywords = "biochemistry, biocontrol, biotechnology, cellular biophysics, enzymes, topology, transient response, design tradeoffs, synthetic gene control circuit, metabolic networks, metabolism, metabolic steady state, regulatory topology, design parameters, transcriptional control circuit, unbranched metabolic pathway, saturable enzyme kinetics, nonoperon topologies, operon topologies, enzyme half-lives, changing metabolic demand, basal enzyme expression, regulatory sensitivity, steady state product bias, Biochemistry, Steady-state, Mathematical model, Genetics, Kinetic theory, Jacobian matrices, Eigenvalues and eigenfunctions",

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

year = "2012",

month = jun,

day = "1",

doi = "10.1109/ACC.2012.6314705",

language = "English",

pages = "2743--2748",

booktitle = "2012 American Control Conference (ACC)",

note = "2012 American Control Conference, ACC 2012 ; Conference date: 27-06-2012 Through 29-06-2012",

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TY - GEN

T1 - Design tradeoffs in a synthetic gene control circuit for metabolic networks

AU - Oyarzún, D. A.

AU - Stan, G.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.

AB - The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.

KW - biochemistry

KW - biocontrol

KW - biotechnology

KW - cellular biophysics

KW - enzymes

KW - topology

KW - transient response

KW - design tradeoffs

KW - synthetic gene control circuit

KW - metabolic networks

KW - metabolism

KW - metabolic steady state

KW - regulatory topology

KW - design parameters

KW - transcriptional control circuit

KW - unbranched metabolic pathway

KW - saturable enzyme kinetics

KW - nonoperon topologies

KW - operon topologies

KW - enzyme half-lives

KW - changing metabolic demand

KW - basal enzyme expression

KW - regulatory sensitivity

KW - steady state product bias

KW - Biochemistry

KW - Steady-state

KW - Mathematical model

KW - Genetics

KW - Kinetic theory

KW - Jacobian matrices

KW - Eigenvalues and eigenfunctions

U2 - 10.1109/ACC.2012.6314705

DO - 10.1109/ACC.2012.6314705

M3 - Conference contribution

SP - 2743

EP - 2748

BT - 2012 American Control Conference (ACC)

T2 - 2012 American Control Conference, ACC 2012

Y2 - 27 June 2012 through 29 June 2012

ER -

Design tradeoffs in a synthetic gene control circuit for metabolic networks

Abstract

Conference

Keywords / Materials (for Non-textual outputs)

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Cite this