Jesko Köhnke

2023 United Kingdom Award Finalist — Faculty

Jesko Köhnke

Current Position:
Professor of Biological Chemistry

Institution:
University of Glasgow

Discipline:
Biophysics and Structural Biology

Recognized for: Using biochemistry and structural biology to study and exploit the biosynthesis of complex natural products—naturally-occurring molecules that often possess antibiotic and anti-cancer activity.

Areas of Research Interest and Expertise: Biological Chemistry, Natural Products, Structural Biology

Previous Positions:

Biochem, Leibniz University Hanover, Germany
Master of Arts, Columbia University, USA
Master of Philosophy, Columbia University, USA
PhD, Columbia University, USA
Postdoctoral Fellow, University of St. Andrews, UK
Junior Group Leader, Helmholtz Institute for Pharmaceutical Research, Germany

Research Summary: The issue of antibacterial resistance looms as one of the great crises facing humanity during the 21st Century. New molecules to treat infection are being discovered at a rapid pace, however, very few possess broad-spectrum activity that is crucial for translation from laboratory to clinic. One class of compounds that shows promising bioactivities are called ribosomally synthesized and post-translationally modified peptides (RiPPs). Jesko Köhnke, PhD studies the production and structural features of these compounds to address pressing medical problems.

RiPPs are initially produced by ribosomes, large biological machines found in living cells primarily responsible for the production of proteins, as short, simple peptides. These peptides serve as a starting point for specialized proteins, enzymes, that perform complex chemical reactions on them. These processes ultimately lead to the creation of RiPPs that have a large variety of bioactivities, including antibiotic as well as anti-cancer and anti-viral. Köhnke is interested in deciphering and exploiting the key enzymatic reactions that transform peptides into RiPPs. His efforts have led to key discoveries about the biosynthesis of two specific RiPPs—bottromycins and thioholgamides. Bottromycins are antibiotics that possess several unique features in their molecular structure and Köhnke discovered key enzymatic reactions responsible for their biosynthesis. These can now be exploited to generate new molecules with improved antibiotic activities. The thioholgamides are RiPPs that display potent anti-cancer activity. Köhnke’s efforts to deduce the biosynthetic pathways responsible for the production of these promising molecules have resulted in a blueprint for future synthetic studies that could result in the production of novel anti-cancer therapeutics.

"The study of enzymes helps us to understand the chemistry of life."

Key Publications: 

  1. Sikandar, M. Lopatniuk, A. Luzhetskyy, R. Müller, J. Koehnke. Total In Vitro Biosynthesis of the Thioamitide Thioholgamide and Investigation of the Pathway. J. Am. Chem. Soc. 2022.
  2. Franz, J. Koehnke. Leader Peptide Exchange to Produce Hybrid, New-to-nature Ribosomal Natural Products. Chem. Commun. 2021.
  3. Sikandar, L. Franz, S. Adam, J. Santos-Aberturas, L. Horbal, A. Luzhetskyy, A.W. Truman, O.V. Kalinina, J. Koehnke. The Bottromycin Epimerase BotH Defines a Group of Atypical α/β-hydrolase-fold Enzymes. Nat. Chem. Biol. 2020.
  4. Franz, S. Adam, J. Santos-Aberturas, A.W. Truman, J. Koehnke. Macroamidine Formation in Bottromycins is Catalyzed by a Divergent YcaO Enzyme. J. Am. Chem. Soc. 2017.

Other Honors: 

2022 Young Investigator Prize for Natural Product Research, DICHEMA

In the Media: 

Chemistry WorldSortase A Strategy Could See Ribosomal Products Reach Further Across Chemical Space

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