Design and Selection of a Synthetic Feedback Loop
for Optimizing Biofuel Tolerance
Version 2 2017-10-12, 13:36
Version 1 2017-10-12, 13:34
Posted on 2017-10-12 - 13:36
Feedback
control allows cells to dynamically sense and respond
to environmental changes. However, synthetic controller designs can
be challenging because of implementation issues, such as determining
optimal expression levels for circuit components within a feedback
loop. Here, we addressed this by coupling rational design with selection
to engineer a synthetic feedback circuit to optimize tolerance of Escherichia coli to the biojet fuel pinene. E. coli can be engineered to produce pinene, but it is toxic to cells. Efflux
pumps, such as the AcrAB-TolC pump, can improve tolerance, but pump
expression impacts growth. To address this, we used feedback to dynamically
regulate pump expression in response to stress. We developed a library
with thousands of synthetic circuit variants and subjected it to three
types of pinene treatment (none, constant, and varying pinene). We
were able to select for strains that were biofuel tolerant without
a significant growth cost in the absence of biofuel. Using next-generation
sequencing, we found common characteristics in the designs and identified
controllers that dramatically improved biofuel tolerance.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Siu, Yik; Fenno, Jesse; Lindle, Jessica M.; Dunlop, Mary J. (2017). Design and Selection of a Synthetic Feedback Loop
for Optimizing Biofuel Tolerance. ACS Publications. Collection. https://doi.org/10.1021/acssynbio.7b00260
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (4)
YS
Yik Siu
JF
Jesse Fenno
JL
Jessica M. Lindle
MD
Mary J. Dunlop
KEYWORDS
circuit variantsE . coliEscherichia coliimplementation issuesbiofuel toleranceexpression impacts growthgrowth costbiojet fuel pinenefeedback circuitOptimizing Biofuel Tolerance Feedback controlSynthetic Feedback Loopfeedback loopEfflux pumpsnext-generation sequencingcircuit componentscontroller designspinene treatmentexpression levels. coli