Doctoral thesis

Dr. Celine Zumkeller:

        »I am fascinated by the genetic blueprint of microorganisms—an archive of hidden possibilities. Harnessing this potential for the bioeconomy is what drives me.«

Microorganisms—that is, bacteria and fungi—serve as biological production systems for a wide variety of chemical compounds. They produce natural substances that we already use today in pharmaceuticals, pesticides, and industrial processes. At the same time, much of their potential remains undiscovered: Their genomes contain blueprints for many more metabolic pathways and molecules that remain invisible under normal laboratory conditions.

Dr. Celine Zumkeller’s doctoral research focuses on this intersection between genetic potential and practical applicability. At the center of her work is the Fraunhofer Biobank, which originated from an industrial strain collection of the pharmaceutical company Sanofi. This biobank is, in a sense, a “treasure trove” of thousands of microorganisms.

Zumkeller established a workflow that uses genomic data to specifically select those strains that are particularly promising for new active compounds or biotechnological processes. Scientifically, the focus was on a previously underexplored group of bacteria, the Acidobacteriota. They are widespread in many soils but are difficult to cultivate in the laboratory. By combining genomics (analysis of genetic information), metabolomics (analysis of metabolic products), and adapted cultivation conditions, the researchers succeeded in “activating” these bacteria. The key signal in this process was the amino acid tryptophan, a typical component of plant excretions. Under the influence of tryptophan, the bacteria increased their metabolic activity, produced more of the plant-active hormone indole-3-acetic acid, and exhibited an inhibitory effect against the wheat pest Zymoseptoria tritici, a major pathogen in wheat cultivation.

The analyses also revealed new, previously uncharacterized biosynthetic gene clusters—that is, gene packages containing the blueprints for complex natural compounds. Many of these clusters are inactive in the natural organism and can only be detected at the genetic level. This raises the question of how such hidden metabolic pathways can be systematically tapped in the future. The HEL modular expression platform was developed as a technical solution to this challenge. This system follows the principles of synthetic biology: promoters (genetic “switches”), regulatory elements, and adaptation modules for various host organisms can be combined in high-throughput settings to specifically activate dormant gene clusters in easily cultivable laboratory organisms. The comprehensive application and validation of large biosynthetic gene clusters is the subject of an ongoing, DFG-funded follow-up project.

For the Fraunhofer Biobank, this work demonstrates how important it is to combine modern metabolomic and genomic methods with classical bioprospecting—that is, the systematic exploration of microbial diversity. Only in this way can the mechanisms behind desired traits be understood, specifically utilized, and evaluated.

To make this hidden world accessible to a broader public, the “Tales of the Tiny” communication series is being launched as a complementary initiative. There, selected strains, their natural compounds, potential applications, and open scientific questions are presented in an engaging way, highlighting the potential hidden within the tiniest inhabitants of our environment.