In this section

Research

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.

Publications

Citation

BibTex format

@article{Gu:2019:10.1016/j.ymben.2018.10.002,
author = {Gu, Y and Lv, X and Liu, Y and Li, J and Du, G and Chen, J and Rodrigo, L-A and Liu, L},
doi = {10.1016/j.ymben.2018.10.002},
journal = {Metabolic Engineering},
pages = {59--69},
title = {Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis},
url = {http://dx.doi.org/10.1016/j.ymben.2018.10.002},
volume = {51},
year = {2019}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - One of the primary goals of microbial metabolic engineering is to achieve high titer, yield and productivity (TYP) of engineered strains. This TYP index requires optimized carbon flux toward desired molecule with minimal by-product formation. De novo redesign of central carbon and redox metabolism holds great promise to alleviate pathway bottleneck and improve carbon and energy utilization efficiency. The engineered strain, with the overexpression or deletion of multiple genes, typically can’t meet the TYP index, due to overflow of central carbon and redox metabolism that compromise the final yield, despite a high titer or productivity might be achieved. To solve this challenge, we reprogramed the central carbon and redox metabolism of Bacillus subtilis and achieved high TYP production of N-acetylglucosamine. Specifically, a “push–pull–promote” approach efficiently reduced the overflown acetyl-CoA flux and eliminated byproduct formation. Four synthetic NAD(P)-independent metabolic routes were introduced to rewire the redox metabolism to minimize energy loss. Implementation of these genetic strategies led us to obtain a B. subtilis strain with superior TYP index. GlcNAc titer in shake flask was increased from 6.6gL−1 to 24.5gL−1, the yield was improved from 0.115 to 0.468g GlcNAc g−1 glucose, and the productivity was increased from 0.274 to 0.437gL−1 h−1. These titer and yield are the highest levels ever reported and, the yield reached 98% of the theoretical pathway yield (0.478gg−1 glucose). The synthetic redesign of carbon metabolism and redox metabolism represent a novel and general metabolic engineering strategy to improve the performance of microbial cell factories.
AU  - Gu,Y
AU  - Lv,X
AU  - Liu,Y
AU  - Li,J
AU  - Du,G
AU  - Chen,J
AU  - Rodrigo,L-A
AU  - Liu,L
DO  - 10.1016/j.ymben.2018.10.002
EP  - 69
PY  - 2019///
SN  - 1096-7176
SP  - 59
TI  - Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis
T2  - Metabolic Engineering
UR  - http://dx.doi.org/10.1016/j.ymben.2018.10.002
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000456420200007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/69069
VL  - 51
ER  -