Discovery and Engineering of Novel Antifungals from Microbiomes

This research area focuses on discovering novel antifungal compounds by exploring microbial communities and ancient microbiomes. It combines bioprospecting with biosynthetic pathway engineering to identify and optimize microbial gene clusters for the production of new bioactive natural products.

The Department Paleobiotechnology (PBT) aims to discover novel antiinfective agents, with a particular focus on antifungal compounds. The rapid spread of multidrug-resistant pathogens, including emerging fungal threats, requires fundamentally new strategies for drug discovery beyond classical screening approaches, which are limited by high rediscovery rates.

We pioneered a new field termed paleobiotechnology, an approach that adds deep evolutionary time to natural product discovery. By analyzing ancient DNA from archaeological materials such as dental calculus, we reconstruct prehistoric microbiomes and identify ancient biosynthetic gene clusters and antimicrobial peptide genes. These genes are synthetically reconstructed and expressed in modern microbial hosts, allowing us to resurrect and access previously untapped chemical diversity with antiinfective potential.

In parallel, we study polymicrobial and inter-kingdom interactions as drivers of secondary metabolite evolution. Using advanced imaging techniques, we visualize interactions between bacteria, fungi, and eukaryotic predators, with a particular focus on amoeba–bacteria predator–prey systems. By combining genome mining, fermentation, and state-of-the-art analytical chemistry, we identify and characterize natural products that function as chemical defenses and frequently display antifungal activity. Together, our work develops evolution-informed, ecology-driven routes toward next-generation antiinfective drug discovery.

We are seeking an excellent and enthusiastic postdoctoral researcher with a strong interest in the discovery of novel antifungal agents.

The Department Biomolecular Chemistry (BMC) integrates genome-driven natural product discovery, biosynthetic pathway analysis, and chemical biology to explore the rich metabolic potential of bacteria and fungi, with a focus on antiinfectives. By combining genome mining with state-of-the-art metabolomics, structural elucidation, and synthetic biology, the group uncovers cryptic secondary metabolites and dissects the enzymatic logic behind their formation. This multidisciplinary approach not only reveals potential drug candidates but also enables pathway engineering to generate structurally diverse molecules with potential therapeutic relevance.

A major research direction of the department is the combination of genome mining with microbial ecology to harness metabolic diversity. The BMC investigates the molecular dialogues that occur in microbial interactions – whether competitive, cooperative, or symbiotic – and identifies the metabolites that mediate these processes. Through co-culture experiments, ecological modeling, and studies of host-associated microbes, the lab uncovers compounds that are activated only in the presence of specific partners and elucidates their roles in virulence, defense, and interspecies communication. These insights highlight how ecological pressures can unlock otherwise silent biosynthetic gene clusters.

Another expanding focus of the BMC is the exploration of anaerobic bacteria and their roles within microbiomes. Supported by advanced genome mining and innovative heterologous expression systems, the group uncovers specialized metabolites and biosynthetic pathways unique to oxygen-intolerant microbes, an area historically neglected due to technical challenges. Because anaerobes dominate many natural and host-associated microbiomes, this work offers a window into how their specialized biosynthetic potential influences microbial community structure and host physiology.