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Synthetic Biology underpins advances in the bioeconomy
Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology.
As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.
@article{Cui:2019:10.1021/acssynbio.9b00140,
author = {Cui, S and Lv, X and Wu, Y and Li, J and Du, G and Ledesma-Amaro, R and Liu, L},
doi = {10.1021/acssynbio.9b00140},
journal = {ACS Synthetic Biology},
pages = {1826--1837},
title = {Engineering a bifunctional Phr60-Rap60-Spo0A quorum-sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis in bacillus subtilis},
url = {http://dx.doi.org/10.1021/acssynbio.9b00140},
volume = {8},
year = {2019}
}
TY - JOUR
AB - Quorum sensing (QS)-based dynamic regulation has been widely used as basic tool for fine-tuning gene expression in response to cell density changes without adding expensive inducers. However, most reported QS systems primarily relied on down-regulation rather than up-regulation of gene expression, significantly limiting its potential as a molecular switch to control metabolic flux. To solve this challenge, we developed a bifunctional and modular Phr60-Rap60-Spo0A QS system, based on two native promoters, P abrB (down-regulation by Spo0A-P) and P spoiiA (up-regulation by Spo0A-P). We constructed a library of promoters with different capacities to implement down-regulation and up-regulation by changing the location, number, and sequences of the binding sites for Spo0A-P. The QS system can dynamically balance the relationship between efficient synthesis of the target product and cell growth. Finally, we validated the usefulness of this strategy by dynamic control of menaquinone-7 (MK-7) synthesis in Bacillus subtilis 168, a model Gram-positive bacterium, with the bifunctional Phr60-Rap60-Spo0A quorum sensing system. Our dynamic pathway regulation led to a 40-fold improvement of MK-7 production from 9 to 360 mg/L in shake flasks and 200 mg/L in 15-L bioreactor. Taken together, our bilayer QS system has been successfully integrated with biocatalytic functions to achieve dynamic pathway regulation in B. subtilis 168, which may be extended for use in other microbes to fine-tune gene expression and improve metabolites production.
AU - Cui,S
AU - Lv,X
AU - Wu,Y
AU - Li,J
AU - Du,G
AU - Ledesma-Amaro,R
AU - Liu,L
DO - 10.1021/acssynbio.9b00140
EP - 1837
PY - 2019///
SN - 2161-5063
SP - 1826
TI - Engineering a bifunctional Phr60-Rap60-Spo0A quorum-sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis in bacillus subtilis
T2 - ACS Synthetic Biology
UR - http://dx.doi.org/10.1021/acssynbio.9b00140
UR - https://www.ncbi.nlm.nih.gov/pubmed/31257862
UR - https://pubs.acs.org/doi/10.1021/acssynbio.9b00140
UR - http://hdl.handle.net/10044/1/71489
VL - 8
ER -