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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{Liu:2018:10.1021/acssynbio.8b00130,
author = {Liu, J and Li, J and Liu, Y and Shin, H-D and Ledesma-Amaro, R and Du, G and Chen, J and Liu, L},
doi = {10.1021/acssynbio.8b00130},
journal = {ACS Synthetic Biology},
pages = {2139--2147},
title = {Synergistic rewiring of carbon metabolism and redox metabolism in cytoplasm and mitochondria of aspergillus oryzae for increased l-Malate production},
url = {http://dx.doi.org/10.1021/acssynbio.8b00130},
volume = {7},
year = {2018}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - l-Malate is an important platform chemical that has extensive applications in the food, feed, and wine industries. Here, we synergistically engineered the carbon metabolism and redox metabolism in the cytosol and mitochondria of a previously engineered Aspergillus oryzae to further improve the l-malate titer and decrease the byproduct succinate concentration. First, the accumulation of the intermediate pyruvate was eliminated by overexpressing a pyruvate carboxylase from Rhizopus oryzae in the cytosol and mitochondria of A. oryzae, and consequently, the l-malate titer increased 7.5%. Then, malate synthesis via glyoxylate bypass in the mitochondria was enhanced, and citrate synthase in the oxidative TCA cycle was downregulated by RNAi, enhancing the l-malate titer by 10.7%. Next, the exchange of byproducts (succinate and fumarate) between the cytosol and mitochondria was regulated by the expression of a dicarboxylate carrier Sfc1p from Saccharomyces cerevisiae in the mitochondria, which increased l-malate titer 3.5% and decreased succinate concentration 36.8%. Finally, an NADH oxidase from Lactococcus lactis was overexpressed to decrease the NADH/NAD+ ratio, and the engineered A. oryzae strain produced 117.2 g/L l-malate and 3.8 g/L succinate, with an l-malate yield of 0.9 g/g corn starch and a productivity of 1.17 g/L/h. Our results showed that synergistic engineering of the carbon and redox metabolisms in the cytosol and mitochondria of A. oryzae effectively increased the l-malate titer, while simultaneously decreasing the concentration of the byproduct succinate. The strategies used in our work may be useful for the metabolic engineering of fungi to produce other industrially important chemicals.
AU  - Liu,J
AU  - Li,J
AU  - Liu,Y
AU  - Shin,H-D
AU  - Ledesma-Amaro,R
AU  - Du,G
AU  - Chen,J
AU  - Liu,L
DO  - 10.1021/acssynbio.8b00130
EP  - 2147
PY  - 2018///
SN  - 2161-5063
SP  - 2139
TI  - Synergistic rewiring of carbon metabolism and redox metabolism in cytoplasm and mitochondria of aspergillus oryzae for increased l-Malate production
T2  - ACS Synthetic Biology
UR  - http://dx.doi.org/10.1021/acssynbio.8b00130
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30092627
UR  - http://hdl.handle.net/10044/1/61893
VL  - 7
ER  -