Bacterial natural products are one of the main sources for the discovery of novel drugs. However, classical cultivation approaches are usually costly and time-consuming and often lead to the rediscovery of known compounds. This is where bioinformatics can help selecting strains and prioritizing biosynthetic gene clusters.
Glycopeptides like vancomycin or teichoplain are antibiotics with activity against Gram-positive bacteria and are currently in clinical use as last resort antibiotics against MRSA infections. The glycopeptide antibiotics (GPAs) are structurally highly diverse. Genome mining studies showed that there is also a huge genetic diversity in the GPA biosynthesis genes and there is a pool of yet unknown GPA-like biosynthetic gene clusters. We use this pool of genomic sequences to study the evolution of GPAs. We are interested in the mechanisms that shaped the GPA diversity, like horizontal gene transfer, recombination, gene gain or loss and genomic rearrangement. We are looking for patterns in the distribution of GPAs throughout the bacterial kingdom and study how acquisition of a GPA biosynthetic gene cluster affects changes in the primary metabolism of the producer strains. In collaboration with the AG Stegmann we aim at identifying new structures and learn how to effectively manipulate GPA scaffolds.
A huge variety of biosynthetic gene clusters is hidden in the “uncultivable” microbial world. We are trying to tap into this source by soil metagenome sequencing and heterologous expression of metagenomic biosynthetic gene clusters. In collaboration with the Group of Geoecology in Tübingen we regularly probe our study sites at the Schönbuch forest in Tübingen to get an overview on biosynthetic gene diversity in different soil communities, depending on the physicochemical properties of the study sites and the actual sampling conditions. Within the scope of this project a bioinformatic tool for metagenome mining is developed. We work on establishing a computational pipeline to identify candidate microorganisms from diverse microbiomes that have not been cultivated before and have the potential of producing novel compounds. We focus on obtaining near complete metagenome assembled genomes (MAGs) from complex environments, such as soil. We assess their taxonomic novelty and capabilities for producing novel compounds, and identify genes that they encode with the help of metatranscriptomics that they can be used as targets for their isolation. We also examine the metabolic pathways of the identified organisms to provide insights into what needs to be in the medium for them to be cultured.
ECRETed is an EU-H2020 multidisciplinary project involving multiple stakeholders. Goal of project is it to develop novel hybrid molecules with tailor-made properties obtained from the combination of biosynthetic genes of amphiphilic compounds (biosurfactants and siderophores) produced by marine and extremophilic microorganisms. Therefore the ‘mix and match’ approach is used where modular genetic elements will be combined to get new tailor-made compounds based on their amphipathic nature.
A healthy plant microbiome is essential for the plant growth and resistance to pathogens. The plant microbiota cultures the plant during different seasons and a changing environment. But how can they resist such hard times? Since microbes produce a number of bioactive secundary metabolites, we hyopthesize, that these compound play a huge role in stabilizing and shaping the microbiome.
With the Arabidopsis thaliana synthetic community (SynCom) from the lab of Prof. Dr. Eric Kemen, we aim to uncover the interaction network of secondary metabolites produced by SynCom bacteria.