Automated Design of Genetic
Toggle Switches with Predetermined
Bistability
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Abstract
Synthetic biology aims to rationally construct biological
devices
with required functionalities. Methods that automate the design of
genetic devices without post-hoc adjustment are therefore highly desired.
Here we provide a method to predictably design genetic toggle switches
with predetermined bistability. To accomplish this task, a biophysical
model that links ribosome binding site (RBS) DNA sequence to toggle
switch bistability was first developed by integrating a stochastic
model with RBS design method. Then, to parametrize the model, a library
of genetic toggle switch mutants was experimentally built, followed
by establishing the equivalence between RBS DNA sequences and switch
bistability. To test this equivalence, RBS nucleotide sequences for
different specified bistabilities were <i>in silico</i> designed
and experimentally verified. Results show that the deciphered equivalence
is highly predictive for the toggle switch design with predetermined
bistability. This method can be generalized to quantitative design
of other probabilistic genetic devices in synthetic biology