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2016 ; 63
(2
): 329-336
Nephropedia Template TP
Lee JW
; Gyorgy A
; Cameron DE
; Pyenson N
; Choi KR
; Way JC
; Silver PA
; Del Vecchio D
; Collins JJ
Mol Cell
2016[Jul]; 63
(2
): 329-336
PMID27425413
show ga
Synthetic biology is increasingly used to develop sophisticated living devices
for basic and applied research. Many of these genetic devices are engineered
using multi-copy plasmids, but as the field progresses from proof-of-principle
demonstrations to practical applications, it is important to develop single-copy
synthetic modules that minimize consumption of cellular resources and can be
stably maintained as genomic integrants. Here we use empirical design,
mathematical modeling, and iterative construction and testing to build
single-copy, bistable toggle switches with improved performance and reduced
metabolic load that can be stably integrated into the host genome. Deterministic
and stochastic models led us to focus on basal transcription to optimize circuit
performance and helped to explain the resulting circuit robustness across a large
range of component expression levels. The design parameters developed here
provide important guidance for future efforts to convert functional multi-copy
gene circuits into optimized single-copy circuits for practical, real-world use.
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