arrow
Return

Macrolide Biosensor Optimization through Cellular Substrate Sequestration

delete2021-02-08
delete18
delete
OA
AI
C
Corwin Miller
J
Joanne M. L. Ho
S
Sydney E. Parks
M
Matthew R. Bennett *
DOI:10.1021/acssynbio.0c00572delete
deleteOriginal
deleteShare
deleteSave
View PDF
Abstract

Abstract

En 中文
Developing and optimizing small-molecule biosensors is a central goal of synthetic biology. Here we incorporate additional cellular components to improve biosensor sensitivity by preventing target molecules from diffusing out of cells. We demonstrate that trapping erythromycin within Escherichia coli through phosphorylation increases the sensitivity of its biosensor (MphR) by approximately 10-fold. When combined with prior engineering efforts, our optimized biosensor can detect erythromycin concentrations as low as 13 nM. We show that this strategy works with a range of macrolide substrates, enabling the potential usage of our optimized system for drug development and metabolic engineering. This strategy can be extended in future studies to improve the sensitivity of other biosensors. Our findings further suggest that many naturally evolved genes involved in resistance to multiple classes of antibiotics may increase intracellular drug concentrations to modulate their own expression, acting as a form of regulatory feedback.
AI Summary

AI Summary

Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.

Journal

ACS Synthetic Biology cover
ACS Synthetic Biology
IF:
3.9
Papers:
3.9K
Citations:
1.2W

Organization

R
Rice University
Scholars:
1.4W
Papers: 1.2W
Citations: 2.6W
Cited Papers

Cited Papers

Multi-Mesh-Scale Approximation of Thin Geophysical Mass Flows on Complex Topographies
err2021-01-01
err0
errOAAI
errYih-Chin Tai Yih-Chin Tai; Jeaniffer Vides Jeaniffer Vides; Boniface Nkonga Boniface Nkonga; Chih-Yu Kuo Chih-Yu Kuo
errShare
errSave
Genetic engineering of macrolide biosynthesis: past advances, current state, and future prospects
err2009-11-10
err63
PREAI
errPark, Sung Ryeol; Han, Ah Reum; Ban, Yeon-Hee; Yoo, Young Ji; Kim, Eun Ji; Yoon, Yeo Joon
errShare
errSave
Gold nanostructure matrices by diffraction mask-projection laser ablation: extension to previously inaccessible substrates
err2010-04-06
err0
PREAI
errMarisa Mäder; Susanne Perlt; Thomas Höche; Helena Hilmer; Marius Grundmann; Bernd Rauschenbach
errShare
errSave
Evolution-guided engineering of small-molecule biosensors
err2019-11-28
err109
errOAAI
errSnoek, Tim; Chaberski, Evan K.; Ambri, Francesca; Kol, Stefan; Bjorn, Sara P.; Pang, Bo; Barajas, Jesus F.; Welner, Ditte H.; Jensen, Michael K.; Keasling, Jay D.
errShare
errSave
Geographic distribution of Angiostrongylus cantonensis in wild rats (Rattus rattus) and terrestrial snails in Florida, USA
err2017-05-18
err0
errOAAI
errHeather D. Stockdale Walden; John D. Slapcinsky; Shannon Roff; Jorge Mendieta Calle; Zakia Diaz Goodwin; Jere Stern; Rachel Corlett; Julia Conway; Antoinette McIntosh
errShare
errSave
Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer
err2016-12-20
err0
errOAAI
errTsuyoshi Hata; Yukako Mokutani; Hidekazu Takahashi; Akira Inoue; Koji Munakata; Kazuya Nagata; Naotsugu Haraguchi; Junichi Nishimura; Taishi Hata; Chu Matsuda; Kohei Murata; Tsunekazu Mizushima; Yuichiro Doki; Masaki Mori; Hirofumi Yamamoto
errShare
errSave
Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors
err2018-01-04
err315
errOAAI
errChen, Ye; Ho, Joanne M. L.; Shis, David L.; Gupta, Chinmaya; Long, James; Wagner, Daniel S.; Ott, William; Josic, Kresimir; Bennett, Matthew R.
errShare
errSave
researcher View more