TY - JOUR
T1 - Fundamental Design Principles for Transcription-Factor-Based Metabolite Biosensors
AU - Mannan, Ahmad A.
AU - Liu, Di
AU - Zhang, Fuzhong
AU - Oyarzún, Diego A.
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/10/20
Y1 - 2017/10/20
N2 - Metabolite biosensors are central to current efforts toward precision engineering of metabolism. Although most research has focused on building new biosensors, their tunability remains poorly understood and is fundamental for their broad applicability. Here we asked how genetic modifications shape the dose-response curve of biosensors based on metabolite-responsive transcription factors. Using the lac system in Escherichia coli as a model system, we built promoter libraries with variable operator sites that reveal interdependencies between biosensor dynamic range and response threshold. We developed a phenomenological theory to quantify such design constraints in biosensors with various architectures and tunable parameters. Our theory reveals a maximal achievable dynamic range and exposes tunable parameters for orthogonal control of dynamic range and response threshold. Our work sheds light on fundamental limits of synthetic biology designs and provides quantitative guidelines for biosensor design in applications such as dynamic pathway control, strain optimization, and real-time monitoring of metabolism.
AB - Metabolite biosensors are central to current efforts toward precision engineering of metabolism. Although most research has focused on building new biosensors, their tunability remains poorly understood and is fundamental for their broad applicability. Here we asked how genetic modifications shape the dose-response curve of biosensors based on metabolite-responsive transcription factors. Using the lac system in Escherichia coli as a model system, we built promoter libraries with variable operator sites that reveal interdependencies between biosensor dynamic range and response threshold. We developed a phenomenological theory to quantify such design constraints in biosensors with various architectures and tunable parameters. Our theory reveals a maximal achievable dynamic range and exposes tunable parameters for orthogonal control of dynamic range and response threshold. Our work sheds light on fundamental limits of synthetic biology designs and provides quantitative guidelines for biosensor design in applications such as dynamic pathway control, strain optimization, and real-time monitoring of metabolism.
KW - dynamic pathway regulation
KW - metabolic engineering
KW - metabolite biosensor
KW - model-based design
KW - pathway optimization
KW - transcriptional regulator
UR - http://www.scopus.com/inward/record.url?scp=85031897610&partnerID=8YFLogxK
U2 - 10.1021/acssynbio.7b00172
DO - 10.1021/acssynbio.7b00172
M3 - Article
C2 - 28763198
AN - SCOPUS:85031897610
SN - 2161-5063
VL - 6
SP - 1851
EP - 1859
JO - ACS synthetic biology
JF - ACS synthetic biology
IS - 10
ER -