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Project Topic
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Our world is changing fast! Key global trends are rapid urbanisation, growing and ageing populations, and increased prosperity. This results in depletion of natural and petrochemical resources and climate change, which affects the quality of the environment and people's lives. Therefore, developing a bio-based economy is key to sustain our planet in the long term. Raw materials will have to be recruited from renewable sources. Industrial biotechnology is potentially a very powerful technology in the transition from petrochemical to renewable resources. It uses microorganisms (fermentation) and enzymes (biocatalysts) to convert low-value agricultural residues which are not suitable to serve as foodstuffs into high value products. Microorganisms have the capacity to produce large amounts of building blocks from biomass by their endogenous metabolism. In addition, metabolic engineering is used to construct microorganisms containing cascades of enzymes that make high-value, high-purity, renewable chemicals. Indole is a good example where biotechnological production can make a difference. Indole is an important flavouring compound with the main market in dairy, tea drinks and fine fragrances. It exhibits a floral odor typical for jasmine teas. There is a strong demand for a more cost-efficient and sustainable method for preparing natural indole. Synthetic indole, derived from coal tar, is available at moderate prices, while the highest quality food-grade indole (natural indole) is very highly priced, due to an expensive chemical conversion process. A reduction in production costs will most likely lead to an increased demand from the market. The INDIE project aims to produce indole via microbial fermentation and enzymatic bioconversion. The production system will be inspired on indole produced in nature. Indole is produced in traces by a variety of bacteria as a signaling molecule. It can also be found at low concentrations in plant essential oils (e.g. jasmine oil). In bacteria and plants, indole is derived from the L-Trp biosynthetic pathway. In our project, we will use the bacterium C. glutamicum for the production of indole because it is capable of producing high amounts of L-Trp. The approach to achieve a biotechnological production of indole will be based on the principle of design-build-test-learn-cycle inherent to systems and synthetic biology approaches. A metabolic model, describing all biochemical pathways of C. glutamicum, will be used to design a bacterium that can produce indole in an optimal way. The design will be tuned by using observations on the bacterium as a system, meaning that regulatory bottlenecks and unintended side products will be eliminated. For this purpose, we will design regulatory circuits that guarantee optimal flow of the metabolism to indole. The best indole-producing strain developed in this way will be tested in an industrial setting, to produce flavour-grade indole. More broadly, the computational models and biosynthetic and regulatory building bricks generated in INDIE will be recruited to build a systems and synthetic biology framework for corynebacteria that will be easily extendable to new food ingredients derived from aromatic amino acids, thereby strengthening the potential of these bacteria for sustainable aromatic compound production. INDIE will accelerate technology transfer to the European level, hence opening new markets and strengthening European efforts to achieve sustainable industrial development.
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