The Piel laboratory studies natural product biosynthesis at the chemical, biochemical, and genetic level. A primary research focus is the question of how and where true metabolic novelty can be found and how this knowledge can be used for drug discovery and development. Some key contributions to this research area are: (i) Co-discovery of trans-acyltransferase polyketide synthases (trans-AT PKSs) as a new and widespread family of biosynthetic enzymes, now known to comprise about 40% of all modular PKS systems identified in bacterial genomes and thus a major pathway classes generating bioactive compounds. We also provided major contributions to understanding the enzymology of these enzymes, including the first elucidation of a complete pathway (for the antibiotic bacillaene), the characterization of new enzymatic components, and the development of a method to predict natural product structures from biosynthetic gene clusters. (ii) Discovery of new ribosomal peptide families with unprecedented posttranslational modifications. The biosynthetic enzymes permit for the first time to introduce diverse D-amino acids and beta-amino acids into ribosomal peptides and proteins. These modifications occur in proteusins and spliceotides, two widely distributed but previously unknown natural product families that were discovered in our laboratory. (iii) Discovery of new talented producers, including the first chemically talented producer taxon from "microbial dark matter". These bacteria, members of the uncultivated candidate phylum Tectomicrobia, are chemically comparably rich as actinomycetes and myxobacteria. Work of the Piel group was published in top-level journals, including Nature, Science, Nature Biotechnology, Nature Chemical Biology, Nature Chemistry, Nature Microbiology, PNAS, and Angewandte Chemie. Jörn Piel is a recipient of an ERC Advanced Project and coordinator of a project within the Swiss NRP 72 "Antimicrobial Resistance".
ETH Zürich is one of the premier world research universities (QS ranking 2018: 7th position) with an outstanding research record (including 21 Nobel laureates connected to it) and a current complement of 400 professors. Key strengths of the university are in life sciences, chemistry, engineering, and computer science. The Department of Biology (D-BIOL) of ETH Zurich studies relationships between structure and function at all levels of biological systems. Examples of this include the dependencies of biomolecules and their ligands; the dependencies of biomolecules and cell structure; and the study of processes in cells, tissues and the functioning of entire organisms.
The Piel group will contribute expertise and studies on the discovery of new chemical entities from previously unexplored natural product pathway families and from neglected bacterial taxa and ecosystems. Among the latter are marine microbes, uncultivated bacteria, and host-associated microbes. Their distinct ecology, interactions, and physiology shape metabolic pathways in ways that differ from traditionally studied producer groups. In agreement, we find a high frequency of bioactives with new chemical structures among these organisms. The lab will identify such organisms and biosynthetic pathways using bioinformatics methods, conduct the isolation and structural characterization work, and provide compounds for further pharmacological evaluation to the network.