Molecular Biotechnology

The group of Elke Nevoigt uses cutting-edge techniques of molecular biology and genetics to engineer yeasts and optimize their characteristics for industrial applications. Baker’s yeast (Saccharomyces cerevisiae) has traditionally been used in the industrial production of food and beverages (such as bread, beer and wine). Another wellknown application of this yeast is the production of proteins such as human protein insulin. Nowadays, S. cerevisiae and several other yeast species have also been exploited in the area of industrial biotechnology (also known as “white biotechnology”) for the sustainable production of chemicals, fuels and materials from renewable resources. In this way, the research field helps to address the urgent environmental problems caused by the use of fossil resources in the chemical industry. In the past, our group has mainly focused on broadening the spectrum of raw materials that can be used to feed the yeast S. cerevisiae such as glycerol (inevitable residue from biodiesel production) and D-galacturonic acid (a major component of residues from sugar beet processing). We have also been working on the production of the platform chemical succinic acid from glycerol and CO2. Future work will focus on the utilization of carbon sources that can be obtained from CO2. By producing valuable products from these compounds, we seek to contribute to the reduction in CO2 emission as well as CO2 capture.

The Nevoigt Laboratory is an international leader in the field of glycerol utilization by baker’s yeast for the production of chemicals, particularly succinic acid. Our lab developed the first S. cerevisiae strains able to efficiently utilize glycerol and they formed the basis of interesting novel applications such as the production of various chemicals, yeast biomass and proteins. We have successfully established the CRISPR/Cas9 system as a tool for yeast engineering.

• Glycerol — A DFG project has focused on engineering the central metabolism of baker’s yeast for more efficient growth on glycerol. Glycerol is an attractive source of carbon and energy since its electron density is higher than that of sugars. Apart from yeast biomass, the target chemical is succinic acid, an important precursor for the chemical industry. An attractive aspect of the project is the fact that CO2 can be incorporated into the target product. So far, we achieved a product yield per glycerol consumed that corresponds to 47% of the theoretical maximum (Malubhoy et al, 2022). A recently secured extension project focuses on fundamental research to improve succinic acid production by the yeast S. cerevisiae.
• YEASTDOC — This European Joint Doctoral programme (Marie Skłodowska-Curie Innovative Training Network) trains early-stage researchers in the field of yeast biotechnology. Six academic institutions worked with seven industry and two training partner organizations to offer an international training programme leading to the award of joint PhD degrees. The interdisciplinary, trans-sectoral research topic takes advantage of recent technological developments to link fundamental research in yeasts with new applications in the beverage and white biotechnology sectors.
• YEASTPEC — In this European collaborative project, Constructor University co-ordinated research with partners from VTT Finland, TU Munich, University of Lisbon, and the industrial partner GlobalYeast in Belgium. This project addresses the optimized utilization of sugar beet pulp, an agricultural pectin-rich waste stream, for bioethanol production by engineered baker’s yeast. Our group focused on the co-utilisation of pulp and glycerol. 
• Eco2Phy — Funded by BIS Bremerhaven in collaboration with the company Kaesler Nutrition GmbH (Cuxhaven), this project aimed to establish a more eco-friendly approach to produce the industrial enzyme phytase using yeast as the production organism. Phytase is commonly added to animal feed in order to release inorganic phosphate from an organic phosphate source (phytic acid) which is present in the feed. The current processes for phytase production rely on yeast as a production host and use methanol. One goal of the project was to replace methanol with glycerol. 
• The group leader is author on 56 peer-reviewed publications, two book chapters, seven patent applications, and co-editor of one book and two special issues.

In 2021, the Nevoigt Laboratory consisted of five PhD students, one postdoc, and one technician. The current funding in 2022 originates from the extension of the above-mentioned DFG project.

• Rendulić, T., Mendonça Bahia, F., Soares-Silva, I., Nevoigt, E., Casal, M. (2022) The dicarboxylate transporters from the AceTr Family and Dct-02 oppositely affect succinic acid production in Saccharomyces cerevisiae. J. Fungi 8:822.
• Malubhoy, Z., Mendonça Bahia, F., de Valk, S.C., de Hulster, E., Rendulić, T., Ragas Ortiz, J.P., Xiberras, J., Klein, M., Mans, R., Nevoigt, E. (2022) Carbon dioxide fixation via production of succinic acid from glycerol in engineered Saccharomyces cerevisiae. Microb. Cell Fact. 21:102. 
• Perpelea, A., Martins L.C., Wijaya, A.W., Rippert, D., Klein, M., Angelov, A., Peltonen, K., Teleki, A., Liebl, W., Richard, P., Thevelein, J.M., Takors, R., Sá-Correia, I., Nevoigt, E. (2022) Towards valorization of pectin-rich agro-industrial residues: engineering of Saccharomyces cerevisiae for co-fermentation of D-galacturonic acid and glycerol. Metab. Eng. 69:1-14. 
• Rippert, D., Linguardo, F., Perpelea, A., Klein, M., Nevoigt, E. (2021) Identification of the aldo-keto reductase responsible for D-galacturonic acid conversion to L-galactonate in Saccharomyces cerevisiae. J. Fungi 7:914. 
• Xiberras, J., Klein, M., de Hulster, E., Mans, R., Nevoigt, E. (2020) Engineering Saccharomyces cerevisiae for succinic acid production from glycerol and carbon dioxide. Front. Bioeng. Biotechnol. 8: 566.