MIB Seminar Series — Jesko-Alexander Köhnke (Leibniz Universität Hannover), Wednesday, May 15th, 12 pm at MIB LT, entitled "Ribosomal natural products - basic research and applications” — Host: Christos Pliotas
Abstract: Peptides have a wide array of functions and applications, including as antimicrobial agents, anti-allergy and anti-cancer drugs, in biological signalling and neurodegenerative disease. They are recognized as highly selective and efficacious drug candidates, which are relatively safe and well tolerated by the human body. A major drawback of peptides in drug development however are the difficulties associated with their bespoke modification, which are essential for peptide development. Biotechnology and total synthesis both encounter significant obstacles, especially for peptides containing non-natural amino acids and extensive modifications.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) have emerged as a major superfamily of natural products with exciting bioactivities. Their biosynthesis begins with the expression of a small gene to yield a precursor peptide via the normal ribosomal route. This precursor peptide is then modified by a cascade of enzymes to yield the final natural product. In many RiPP pathways the biosynthetic enzymes have been shown to be highly tolerant of changes to the amino acid sequence of their substrates. The talk will cover basic RiPP research, focussing on in vitro biochemistry and structural biology. These insights can be used for biotechnological applications to generate libraries of bespoke peptides for high-throughput screening and the discovery of novel probes for the development of diagnostics.
Bio: Prof Koehnke is Professor of Natural Product Biotechnology and managing director of the institute of Food Chemistry at Leibniz University Hannover, Germany. After graduating from the biochemistry program at Leibniz University, Hanover, Germany, he obtained a M.A., M.Phil. and PhD from Columbia University, NY, USA, while working on the structural biology of synaptic adhesion (e.g. Proc Natl Acad Sci USA, 2008; Neuron, 2010). In 2010 he joined the group of Prof. James Naismith, FRS (then U. St Andrews, UK), funded by a Wellcome Trust VIP and a German Research Foundation (DFG) post-doctoral fellowship. During that time, he investigated the biosynthesis of the ribosomally synthesized and post-translationally modified peptides (RiPPs) cyanobactins (Nat Struct Mol Biol, 2012; Angew Chem Int Ed Engl, 2013; Nat Chem Biol, 2015). In 2014 Prof. Koehnke received an Emmy Noether Fellowship (DFG) to start his independent career at the Helmholtz Institute for Pharmaceutical Research Saarland (Germany) in 2015. His work focused on structural biology (Nat Comm, 2017; J Am Chem Soc, 2018) and natural product (RiPP) biosynthesis (J Am Chem Soc, 2017, 2019 and 2020; Nat Chem Biol,2020). In 2020 he moved to the School of Chemistry at University of Glasgow (UoG) as a Reader, before being promoted to Professor of Biological Chemistry in 2022. His work continued to focus on the biosynthesis of natural products (e.g. J Am Chem Soc, 2022; Nat Chem,2023; Angew Chem Int Ed Engl, 2024).
