Adverse drug reactions (ADRs) endanger patients' health and pose a challenge to drug development and medical care. Predicting ADRs still fails in many cases due to their idiosyncrasy and limited assay or cross-species translatability. Findings from diverse sources need to be contextualised with individual patient conditions, e.g., diseases, genotypes, or co-medications, to enable a systemic understanding and reliable predictions of ADRs. However, experiments mimicking realistic patient scenarios are often expensive, infeasible, and insufficient. Here, mechanistic in silico models have emerged...

Climate change represents a severe global issue also driven by the consumption of fossil fuels, which ultimately release greenhouse gases into the atmosphere. Simultaneously, the rising demand for food, energy, and chemicals requires a shift from fossil to sustainable raw materials. Utilizing renewable carbon sources (i.e., biomass, CO2, organic waste) ensures a fossil-free future. Over recent years, itaconate has gained increasing interest as a prospective bio-based platform chemical. To replace nowadays petroleum-derived substances like methacrylic acid in industrial applications, enhancing...

Methyl ketones with a hydrocarbon chain length of C4 to C17 are currently produced from petrochemical resources, and there is only limited research on sustainable production and purification of those in the scope of a circular bioeconomy. This work elucidates sustainable bioprocesses to produce methyl ketones. For this, microbial production of methyl ketones was integrated into the preceding and consecutive process steps and optimized beyond the isolated figures of merit.

Building a sustainable society requires moving beyond the linear produce-use-waste model reliant on fossil resources. A circular bioeconomy using CO2-derived one carbon (C1) molecules as feedstocks could be a potential alternative. This work explores the methylotrophic yeast Ogataea polymorpha as a production platform for the conversion of the C1 molecules methanol and formate into industrially relevant low molecular weight biochemicals.

Ginseng is a traditional plant in Chinese medicine because it includes pharmaceutical ginsenosides that have been used in Asia for thousands of years. Ginsenosides are triterpenoids, a class of natural products mainly present in Panax species (e.g., Panax ginseng, P. notoginseng, and P. quinquifolium). However, due to the shortcomings of chemical synthesis and extraction from plants, the synthesis of ginsenosides by microbial cell factories, which has the advantages of environmental friendliness, high efficiency, convenience, and potentially low cost, has received much attention in recent...

Triterpenoids are plant secondary metabolites with wide application fields. Their production in microbial cell factories is a more advantageous alternative to the existing processes. This work focusses on gaining insights into cell performance for an optimal process design. For this, a novel analytical method and a strategy to overcome limitations caused by intracellular product accumulation, and for simplification of the downstream process were evaluated.

Biosurfactants are sustainable alternatives to synthetic surfactants. Bioprocesses were developed for glycine-glucolipids from Alcanivorax borkumensis and rhamnolipids with recombinant Pseudomonas putida. Excessive foam formation was addressed using optimized aeration strategies and a novel dynamic membrane stirrer. Improved media and feeding strategies enhanced glycolipid yields, while foam-free rhamnolipid production achieved high space-time yields, advancing industrial applicability.

Phosphate (Pi) is an irreplaceable nutrient in all living organisms and is mined from Pi rock. Since the global Pi rock reserves will be depleted in a few hundred years, it is essential to develop new strategies for recycling Pi from unused Pi waste streams. One such Pi waste stream is plant biomass, a by-product of the deoiling of seeds and bran. In addition, unused Pi accumulates in various waste streams during the production of Pi rich molecules. In this thesis, Pi was recycled from these waste streams into polyphosphate (polyP). Therefore, Pi-starved Saccharomyces cerevisiae was subjected...

A novel microbial chassis from Paracoccus spp. was developed to support circular bioeconomy goals. A genetic toolbox enabling PET monomer utilization was constructed. Whole-genome sequencing led to reclassification of uncharacterized strains. Metabolic flux analysis and a curated genome-scale model (iPpan24) revealed ED pathway preference and predicted product yields, enabling model-guided strain engineering.

Polymalate (PMA), a promising drug delivery system, can be produced by Aureobasidium pullulans NRRL 62031. The key genetic determinant for PMA polymerization and the primary pathway for malate synthesis were identified. Four gene knockout targets and one overexpression target were found to enhance PMA titer. Genetic insights into PMA hydrolysis were also obtained through bioinformatics. This study lays the foundation for the large-scale production of PMA and its medical applications.