Synthetic metabolic route allows optimal use of xylose for bio-production of chemicals

Scientists from Toulouse, France, genetically modified Escherichia coli in order to assimilate (d)-xylose and direct it towards commercially interesting compounds in a novel manner.


Early, this July I attended the Synthetic and Systems Biology School in Taormina, Italy. Apart from the lectures and poster sessions, selected talks from the participants were also presented. Amongst others, I distinctly remember two postdoctoral researchers, Ceren and Débora, who enthusiastically described their work about producing interesting chemicals in E. coli. I was therefore very pleased when I saw their paper published in ACS Synthetic Biology a few weeks ago.

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      Native (blue) and synthetic (green) (D)-xylose assimilation pathway. The chemicals of interest (pink) and the first steps of glycolysis are also noted. The green numbers represent the heterologous enzymes that were used. Figure adapted with permission from Cam et al., 2015. Copyright American Chemical Society (2015).   


Native (blue) and synthetic (green) (D)-xylose assimilation pathway. The chemicals of interest (pink) and the first steps of glycolysis are also noted. The green numbers represent the heterologous enzymes that were used. Figure adapted with permission from Cam et al., 2015. Copyright American Chemical Society (2015).   

This article narrates a nice metabolic engineering approach to introduce a novel (D)-xylose assimilation metabolic route in E.coli. Naturally, E.coli phosphorylates (D)-xylose at C5 and incorporates it into the main metabolism. What the designed pathway does is assimilate the (D)-xylose through C1 phosphorylation, bypassing the pentose phosphate pathway and its native regulation. The sugars can now be introduced in the glycolysis pathway and thus be used for organism growth, while the desired chemical products are produced in a more targeted manner by expressing the respective biosynthetic enzymes. The theoretical product yields were computed and compared to the native metabolism and other engineering approaches, the novel enzymes that need to be expressed were identified and characterised, and microarray experiments and metabolite analysis were carried out to study the organism’s response to the new pathway. Finally, selected chemicals were produced by dedicated strains that performed impressively in terms of yields and product concentration.

So what's missing? It would be informative to see how the strains behave and what titres can be achieved in large batch-fermentation experiments. There is a small loss of growth rate of the modified strains. Moreover, it would be interesting to optimise the strains further and to test how generic this approach is by transferring the pathway to other organisms, such as baker’s yeast. Overall, however, this research paper is an easy-to follow biotechnology story that begins with the motivation and design and reaches the desired outcome of increased product formation.

There are two take-home messages that I would like to address after reading this article. The first comes from the use of (D)-xylose as a substrate. The rationale behind it is that xylose constitutes a large proportion of the unused cellulose and hemicellulose biomass that are byproducts of bio-refinery. This is a prime example of synthetic biology employed in sustainability efforts, where a waste product is converted into commercially interesting compounds. Those formed products are currently available in industrial scale as fossil fuel byproducts and their production using E.coli is an environmentally friendlier alternative. However, the bio-sustainability argument has some pitfalls and needs to be employed carefully. A fermentation production is itself an energy consuming process. Also, the use of sugars should not directly compete with or use up agriculture resources. Nevertheless, it is my opinion that the industry needs to disengage fast from oil as a feedstock, and synthetic biology is a powerful tool that can provide novel alternatives.

A second point is the use of systems biology together with synthetic biology. Taking into account that a system cannot be simply described by the addition of its components but also requires the interactions between those parts, likewise a bioengineering approach cannot rely on the simple expression of a heterologous pathway and the optimisation of the participating enzymes. This principle is illustrated in this article, where metabolic modelling and microarray analysis that provide invaluable insights during the pathway design and the strain optimisation steps respectively. Interdisciplinary research is also present in this work, as computational science, bioinformatics, and analytical chemistry are employed together with molecular biology and biochemistry. It becomes more and more obvious that single-focus and narrow approaches are getting obsolete. The new generation of scientists needs to speak the language of and understand collaborators coming from different backgrounds. Synthetic biology, which in principle combines parts to obtain new properties and novel functions, cannot fall behind in combining different disciplines in a way that facilitates research and strengthens innovation and creativity.



Research Paper: 

Yvan Cam, Ceren Alkim, Debora Trichez, Vincent Trebosc, Amélie Vax, François Bartolo, Philippe Besse, Jean Marie François, and Thomas Walther (2015) Engineering of a Synthetic Metabolic Pathway for the Assimilation of (d)-Xylose into Value-Added Chemicals. ACS Synthetic Biology DOI: 10.1021/acssynbio.5b00103


Written by:

Konstantinos Vavitsas

Konstantinos is a PhD student at the University of Copenhagen, working on the photosynthetic production of high-value compounds. 

Edited by: Devang Mehta


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