Genetic engineering for natural product discovery and production
Our research group applies molecular biological, chemical and process engineering approaches for the discovery and production of natural substances with therapeutic potential.
Previous and Current Research
The emergence of multi-resistant pathogens represents a serious threat to global health. Since conventional antibiotics are increasingly losing their effectiveness against these pathogens, there is great societal interest in the discovery of new antimicrobial agents. For the development of most antibiotics used in the medical field, microbial natural substances served as the starting point. Through the use of modern and efficient sequencing technologies, genomes of microorganisms are continuously decoded. Many of these genomes contain numerous genes for the synthesis of complex organic compounds with most of them exhibiting biological activity, the so-called secondary metabolites. However, there is often a large discrepancy between the number of annotated biosynthetic genes and the deciphered natural products of the respective microorganism, since the formation of these substances often does not occur under laboratory conditions. In particular, social amoebae such as Dictyostelium discoideum have great potential for the discovery of new active ingredients due to their genetic repertoire. Using means of synthetic microbiology, we aim to disclose cryptic biosynthetic pathways in order to discover new natural products for drug discovery. This research includes the targeted activation or extrachromosomal expression of secondary metabolite routes followed by subsequent process optimization in bioreactors to generate sufficient quantities of target substances for structural and functional elucidation.
Furthermore, we aim to assess the general suitability of the amoeba D. discoideum to serve as a chassis for the synthesis of plant-derived active substances. Inspired by the fact that the amoeba possesses several enzymatic functions that are usually found in plants, we utilize multi-gene expression systems for the construction of heterologous biosynthetic pathways and microbial production of active pharmaceutical ingredients in amoeba. We already demonstrated that amoeba-based processes can be transferred to industrial scales and will further exploit that knowledge to develop novel bioprocesses.
Future Projects and Aims
Our research comprises three main areas: i) development of CRISPR activation-based strategies for targeted activation of biosynthetic pathways in various microbial host systems, ii) discovery and characterization of new secondary metabolites, and iii) heterologous production of pharmaceutically relevant substances using metabolic engineering of the social amoeba Dictyostelium discoideum.