Many pharmaceuticals are derived from microbial natural products; hence the discovery of novel bioactive compounds is often the basis for the development of new drugs. Microbial natural products possess diverse chemical structures, and they are categorised into different classes based on the building blocks, e.g., polyketides, peptides, and terpenes. Our lab focuses on peptides from microbial specialised metabolism.
Peptide structures are found in many biologically active substances, and they generally play important roles in the metabolism, for example as hormones or neurotransmitters. The two large groups of peptide natural products are classified based on their biosynthesis: non-ribosomal peptides are produced by large mega-enzymes, the non-ribosomal peptide synthetases (NRPS), and RiPPs (ribosomally synthesised and post-translationally modified peptides) are produced by the ribosomal pathway: the precursor protein (consisting of leader and core peptide), post-translationally acting maturases, and proteases/transporters are individually produced at the ribosome. Afterwards, the core peptide of the precursor protein is modified by the maturases before the protease cleaves the precursor protein to yield the mature peptide natural product.
We use genome mining to identify novel RiPP biosynthetic gene clusters and investigate these biosynthetic pathways focussing on the biochemical characterisation of the involved enzymes and on their potential for peptide engineering. Our lab combines approaches from different fields and consists of chemists, biologists, biochemists, pharmacists, and microbiologists.