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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{Lv:2020:10.1016/j.ymben.2020.02.003,
author = {Lv, X and Wu, Y and Tian, R and Gu, Y and Liu, Y and Li, J and Du, G and Ledesma-Amaro, R and Liu, L},
doi = {10.1016/j.ymben.2020.02.003},
journal = {Metabolic Engineering},
pages = {106--118},
title = {Synthetic metabolic channel by functional membrane microdomains for compartmentalized flux control},
url = {http://dx.doi.org/10.1016/j.ymben.2020.02.003},
volume = {59},
year = {2020}
}
TY - JOUR
AB - The anchoring of metabolic pathway enzymes to spatial scaffolds can significantly improve their reaction efficiency. Here, we successfully constructed a multi-enzyme complex assembly system able to enhance bioproduction in bacteria by using the endogenous spatial scaffoldsfunctional membrane microdomains (FMMs). First, using VA-TIRFM and SPT analysis, we reveal that FMMs possess high temporal and spatial stability at the plasma membrane and can be used as endogenous spatial scaffolds to organize enzyme pathways. Then, taking the synthesis of N-acetylglucosamine (GlcNAc) in Bacillus subtilis as a proof-of-concept demonstration, we found that anchoring of various enzymes required for GlcNAc synthesis onto FMMs to obtain the FMMs-multi-enzyme complex system resulted in a significant increase in GlcNAc titer and an effectively alleviate in cell lysis at the later stage of fermentation compared to that in control strains expressing the related enzymes in the cytoplasm. Combining with metabolic model and kinetics analysis, the existence of a constructed substrate channel that maximizes the reaction efficiency is verified. In summary, we propose a novel metabolic pathway assembly model which allowed improved titers and compartmentalized flux control with high spatial resolution in bacterial metabolism.
AU - Lv,X
AU - Wu,Y
AU - Tian,R
AU - Gu,Y
AU - Liu,Y
AU - Li,J
AU - Du,G
AU - Ledesma-Amaro,R
AU - Liu,L
DO - 10.1016/j.ymben.2020.02.003
EP - 118
PY - 2020///
SN - 1096-7176
SP - 106
TI - Synthetic metabolic channel by functional membrane microdomains for compartmentalized flux control
T2 - Metabolic Engineering
UR - http://dx.doi.org/10.1016/j.ymben.2020.02.003
UR - https://www.ncbi.nlm.nih.gov/pubmed/32105784
UR - http://hdl.handle.net/10044/1/78003
VL - 59
ER -