Targeted biosynthesis of bioactive, commercially viable triterpenoids

Triterpenoids are one of the largest and most diverse groups of natural products found in plants, with thousands of known compounds. Plants use triterpenoids for specialized roles, such as pest defense and pollinator attraction, rather than for primary growth. Their complex structures arise from over 100 triterpene scaffolds that can be modified further to create remarkable chemical diversity.
Many cyclic triterpenoids exhibit antimicrobial, antioxidant, anticancer, and anti-allergic properties, making them promising candidates for agricultural, pharmaceutical, and cosmetic applications. However, extracting them from plants is resource-intensive and delivers variable yields, and is often unsuitable for  large-scale, sustainable production. Chemical synthesis is also challenging due to the compounds' structural complexity and the formation of unwanted byproducts. 
In line with the bioeconomy, there is a need for sustainable, alternative production and purification systems.
For many years, we have focused on the biosynthesis of triterpenoids in yeast.

Discover our patented yeast platform, Saccharomyces cerevisiae, the smart solution for the sustainable, scalable production of high-quality, plant-based natural compounds.

The benefits

• Sustainable and reliable production Transferring knowledge about plant enzymes to the robust microbial cell factory Saccharomyces cerevisiae enables the production of active ingredients of consistently high quality while conserving resources.
• Complex replication of plant metabolic pathways The platform enables the complete recombinant production of natural plant intermediates and end metabolites, including complex oxidation and glycosylation steps.
• High yields and scalability Through optimized fermentation processes (fed-batch) and genetic modification of regulatory networks, we achieve product concentrations in the gram range (up to 10% of the cell mass).
• Modularity for various active ingredients The patented platform can be flexibly expanded to include monoterpenes and sesquiterpenes, with a particular focus on anti-inflammatory and antimicrobial active ingredients.
• Safety and regulatory advantages (GRAS status) As a well-characterized GRAS ("Generally Recognized as Safe") organism, baker's yeast significantly facilitates the regulatory approval of the produced active ingredients—a decisive advantage for medical and cosmetic applications.

Contact us for a customized solution for your bioactive ingredient!

Project objectives and structure

This project forms part of the “Tailor-made bio-based ingredients for a competitive bioeconomy” funding programme of the Federal Ministry of Research, Technology and Space (BMBF), as well as the National Research Strategy Bioeconomy 2030.

The R&D consortium is coordinated by Fraunhofer IME and includes additional partners such as the Technical University of Munich (TUM), as well as the SMEs Phytowelt GreenTechnologies GmbH and VivaCell Biotechnology GmbH.

Research background

Triterpenoids are of great economic interest due to their diverse biological activities, such as anti-inflammatory and anti-tumour properties. The main objective of the 'Perspective' project is to develop pharmacologically relevant triterpenoids through targeted biological synthesis. This will be achieved through biocatalysis and fermentation on a yeast-based platform. The project aims to exploit the structure–activity relationships of these bioactive substances to enable applications in the fields of pharmaceuticals, cosmetics and agriculture.

Progress and results
As part of the “Perspective” project, we made significant progress in the application of triterpenoids and understanding their effects. In the areas of gene identification and expression, we developed a platform for the oxidation and glycosylation of triterpenoids. The optimization of yeast strains enabled the production of relevant quantities of oxidized triterpenes on a gram scale. We demonstrated the feasibility of glycosylation both in vivo and in vitro, which can now be scaled up. For downstream processing, we optimized chromatographic separation by fractional extraction of the triterpenoids, enabling us to isolate them with a purity of over 98 percent (NMR tested).
In biological tests, the isolated triterpenoids showed significant activity in pharmacologically relevant experiments, such as inflammation assays. They also demonstrated a positive effect on the digestive tract in model systems.
We compiled a priority list that ranks triterpenoids intended for further diversification strategies through enzymatic catalysis in yeast.  Through metabolic analysis, we identified additional ways to optimise yeast strains and modify fermentation conditions to boost triterpenoid production, employing 13C labelling and subsequent testing. We are currently conducting experiments to track the metabolism of applied triterpenoids in a cell model.

Outlook and future steps
The triterpenoids developed in this project will be evaluated in collaboration with industrial partners across various application areas, including animal feed, bioactives, cosmetics and pharmaceuticals. This will facilitate their timely integration into the approval process.

Conclusion
The project has achieved significant scientific progress while concurrently creating sustainable value in accordance with the national Bioeconomy 2030 research strategy, the German sustainability strategy, and the United Nations Sustainable Development Goals (UN SDGs). The results of the study indicate the potential for triterpenoids to be used industrially in the future.