Birgitta Ebert

Microbial fatty acid derivative production from CO2-derived intermediates

This project uses synthetic biology to develop microbial fermentation for producing fatty acid derivatives from CO2-derived acetate/ethanol. Target molecules include methyl ketones for aviation fuel, plasticizers, and monomers, addressing critical gaps in renewable chemical production for a sustainable industry.

Brewing natural products with yeast

The yeast Saccharomyces cerevisiae is widely used in fermentation to produce wine, beer, and bioethanol. However, this well-researched microbe can also be efficiently engineered for the production of complex natural products. Well-known examples are the anti-malaria drug artemisinin are the ant-cancer drug paclitaxel.

In this project, we are interested in the production of triterpenoids, the largest group in the natural product class. Many of these molecules have biological activities that make them promising candidates for pharma, nutraceutical, or cosme(ceu)tical applications.

We have engineered a superior S. cerevisiae platform strain capable of the synthesis of diverse triterpenoids at the gram-scale level. In this project, we aim to expand the product spectrum to alpha-amyrin type triterpenoids with anti-ageing and anti-obesity properties that are used are investigated for use in cosmetics and pharmaceuticals.

You will recombinantly express plant enzymes in the yeast chassis to enable the production of a few target products. You will further address a major bottleneck in the production of triterpenoids, the intracellular accumulation of the products, which results in cell toxification and low production efficiency. We are following alternative and complementary approaches including the expression of recently identified transporter, in situ extraction and optimization of the intracellular product trafficking route.

You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microscopy, fermentation, and analytics.

Honours and (under)graduate students are welcomed to work on specific subprojects.

Please contact me for further information.

Vaccine adjuvant production in tailored yeast

Modern protein-based vaccines require adjuvants to improve immunogenicity and hence efficacy. The natural product class of triterpenoids includes molecules that have been shown to be very potent vaccine adjuvants. From these candidates, squalene and Quillaja saponins have been approved for their use in vaccines against flu, shingles and malaria. And many more triterpenoid-adjuvanted vaccines are in the pipeline.

These molecules are currently sourced from animal and plant-derived sources. Squalene is found in high abundance in the liver oil from (deep-sea) sharks and currently the only approved source for medical applications. The Quillaja saponins contained in QS-21 adjuvants are only produced by specific trees in limited regions in South America. Both species, sharks and Quillaja saponaria, are threatened by overexploitation. With the increasing demand for potent vaccines, this is expected to increase.

In this project, we are working on the biotechnological production of these compounds with engineered Baker's yeast Saccharomyces cerevisiae. We can produce squalene and QS-21 precursors at the gram-scale level, which is the current state of the art.

Within this larger project, two HDR projects are available focusing on (a) improving squalene production and secretion of the intracellular storage molecule into the fermentation medium, and (b) implementing the complex QS-21 biosynthesis pathways in the yeast chassis.

Honours and (under)graduate students are welcomed to work on specific subprojects.

You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microbiological work, fermentation, and analytics.

Please contact me for further information.

Redox engineering for carbon-efficient biotechnological processes

Redox cofactors play a central role in the metabolism of living organisms. The most widely used cofactor is NAD(P)H. In the central carbon metabolism, the oxidised form NAD(P)+ is the primary acceptor for electrons from carbon oxidation. These electrons are then fed into the electron transfer chain, powering the respiratory system for ATP and thus energy generation. Although efficient, this system leads to CO2 formation via the oxidation of carbon metabolites and, hence, to CO2 emissions during biotechnological processes. In this project, we investigate alternative systems for NADH regeneration with electrons from sustainable energy sources, ultimately decoupling energy and carbon metabolism. Our focus lies hereby on hydrogenases. These enzymes use electrons from hydrogen to generate NADH instead of carbon metabolites, while hydrogen can be produced solely from water and electrons from renewable energy sources. Implementing efficient hydrogenase-based NADH regeneration systems in vivo should lead to more carbon-efficient and sustainable biotechnological processes for a greener bio-based future.

We’re looking for a motivated student interested in carbon-efficient biological processes. The project offers options for working in molecular biology, bioprocess development, and robotics. Please get in touch with me for further information.