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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{Xu:2020:10.1038/s41589-020-0637-3,
author = {Xu, X and Li, X and Liu, Y and Zhu, Y and Li, J and Du, G and Chen, J and Ledesma-Amaro, R and Liu, L},
doi = {10.1038/s41589-020-0637-3},
journal = {Nature Chemical Biology},
pages = {1261--1268},
title = {Pyruvate-responsive genetic circuits for dynamic control of central metabolism},
url = {http://dx.doi.org/10.1038/s41589-020-0637-3},
volume = {16},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Dynamic regulation is a promising strategy for fine-tuning metabolic fluxes in microbial cell factories. However, few of these synthetic regulatory systems have been developed for central carbon metabolites. Here we created a set of programmable and bifunctional pyruvate-responsive genetic circuits for dynamic dual control (activation and inhibition) of central metabolism in Bacillus subtilis. We used these genetic circuits to design a feedback loop control system that relies on the intracellular concentration of pyruvate to fine-tune the target metabolic modules, leading to the glucaric acid titer increasing from 207 to 527 mg l−1. The designed logic gate-based circuits were enabled by the characterization of a new antisense transcription mechanism in B. subtilis. In addition, a further increase to 802 mg l−1 was achieved by blocking the formation of by-products. Here, the constructed pyruvate-responsive genetic circuits are presented as effective tools for the dynamic control of central metabolism of microbial cell factories.
AU  - Xu,X
AU  - Li,X
AU  - Liu,Y
AU  - Zhu,Y
AU  - Li,J
AU  - Du,G
AU  - Chen,J
AU  - Ledesma-Amaro,R
AU  - Liu,L
DO  - 10.1038/s41589-020-0637-3
EP  - 1268
PY  - 2020///
SN  - 1552-4450
SP  - 1261
TI  - Pyruvate-responsive genetic circuits for dynamic control of central metabolism
T2  - Nature Chemical Biology
UR  - http://dx.doi.org/10.1038/s41589-020-0637-3
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000566865800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41589-020-0637-3
UR  - http://hdl.handle.net/10044/1/82966
VL  - 16
ER  -