Metabolic engineering of thermophilic clostridia for production of dicarboxylic acids


In order to reduce our dependence on fossil fuels it is not only important to find alternative energy sources, but also to find alternative ways to produce our goods and chemicals that are currently derived from petroleum.

One way to do this is by using microorganisms to convert biomass, which is typically a complex mixture of sugar polymers, into useful chemicals, or building blocks. Examples of those building blocks are aspartic acid, glycerol and succinic acid. It is important that there’s no competition with food production, hence it’s desired to use waste biomass (from agriculture), which is generally hard to degrade and requires an additional pretreatment step with enzymes.

Most existing large scale fermentation processes use well studied organisms, such as S. cerevisiae, E. coli, C. glutamicum and A. niger.  All of these often-used organisms are so called mesophilic organisms, which grow at moderate temperatures (30 – 40 degrees). However, in industrial processes it can have many advantages to use thermophilic organisms, which can grow at much higher temperatures. The main advantages are that a process with a thermophile (1) requires less cooling, (2) has a lower risk of contaminations, and (3) has the possibility to use the biomass-degrading enzymes simultaneously with the fermentation step, simplifying the whole process.

Dicarboxylic acids, such as succinic acid have a lot of potential as chemical building blocks for the production of polymers, resins, and solvents. In order to compete with similar, fossil fuel-derived products, the production costs need to be very low, which is a big technical challenge. As the potential applications of succinic acid are all very high volume products, solving this challenge might contribute significantly in decreasing our dependence on fossil fuels. And one way to help solve it could be to explore the use of thermophiles.


The aim of the project is the metabolic engineering of thermophilic clostridia for the production of dicarboxylic acid. More specifically, the project focusses on Clostridium thermosuccinogenes for the production of succinic acid. C. thermosuccinogenes is the only known thermophile that naturally produces large amounts of succinic acid (along with several other products). It is therefore interesting, not just to use C. thermosuccinogenes for the production of succinic acid, but also to study its metabolism, as the gained knowledge (or even specific genes) can then be used when engineering other (perhaps better studied/suited) organisms for the production of succinic acid, such as Clostridium thermocellum.

Bsc/Msc thesis:

A thesis project could include a broad range of techniques, such as genetic engineering, enzymatic assays, (anaerobic) fermentations, or even modeling, depending on the advancement of the project and the interests of the student.

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