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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{Niu:2021:10.1002/bit.27577,
author = {Niu, T and Lv, X and Liu, Y and Li, J and Du, G and Ledesma-Amaro, R and Liu, L},
doi = {10.1002/bit.27577},
journal = {Biotechnology and Bioengineering},
pages = {383--396},
title = {The elucidation of phosphosugar stress response in Bacillus subtilis guides strain engineering for high N-acetylglucosamine production.},
url = {http://dx.doi.org/10.1002/bit.27577},
volume = {118},
year = {2021}
}

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RIS format (EndNote, RefMan)

TY - JOUR
AB - Bacillus subtilis is a preferred microbial host for the industrial production of nutraceuticals and a promising candidate for the synthesis of functional sugars, such as N-acetylglucosamine (GlcNAc). Previously, a GlcNAc-overproducer Bacillus subtilis SFMI was constructed using glmS ribozyme dual regulatory tool. Herein, we further engineered to enhance carbon flux from glucose towards GlcNAc synthesis. As a result, the increased flux towards GlcNAc synthesis triggered phosphosugar stress response, which caused abnormal cell growth. Unfortunately, the mechanism of phosphosugar stress response had not been elucidated in B. subtilis. In order to reveal stress mechanism and overcome its negative effect in bioproduction, we performed comparative transcriptome analysis. The results indicate that cells slow glucose utilization by repression of glucose import and accelerate catabolic reactions of phosphosugar. To verify these results, we overexpressed the phosphatase YwpJ, which relieved phosphosugar stress and allowed us to identify the enzyme responsible for GlcNAc synthesis from GlcNAc6P. In addition, the deletion of nagBB and murQ, responsible for GlcNAc precursor degradation, further improved GlcNAc synthesis. The best engineered strain, B. subtilis FMIP34, increased GlcNAc titer from 11.5 to 26.1 g/L in shake flasks and produced 87.5 g/L GlcNAc in 30-L fed-batch bioreactor. Our results not only elucidate, for the first time, the phosphosugar stress response mechanism in B. subtilis, but also demonstrate how the combination of rational metabolic engineering with novel insights into physiology and metabolism allows the construction of highly efficient microbial cell factories for the production of high value chemicals. This article is protected by copyright. All rights reserved.
AU - Niu,T
AU - Lv,X
AU - Liu,Y
AU - Li,J
AU - Du,G
AU - Ledesma-Amaro,R
AU - Liu,L
DO - 10.1002/bit.27577
EP - 396
PY - 2021///
SN - 0006-3592
SP - 383
TI - The elucidation of phosphosugar stress response in Bacillus subtilis guides strain engineering for high N-acetylglucosamine production.
T2 - Biotechnology and Bioengineering
UR - http://dx.doi.org/10.1002/bit.27577
UR - https://www.ncbi.nlm.nih.gov/pubmed/32965679
UR - https://onlinelibrary.wiley.com/doi/10.1002/bit.27577
UR - http://hdl.handle.net/10044/1/83213
VL - 118
ER -