Professor Thomas Poulsen and colleagues from the Department of Chemistry, Aarhus University, together with Associate Professor Thomas Tørring from the Department of Biological and Chemical Engineering, have published exciting new findings in Angewandte Chemie International Edition. The work highlights the value of cross-disciplinary collaboration at Aarhus University.

The researchers have discovered a previously unknown enzymatic step in the biosynthesis of lysocellin – a natural compound with antimicrobial properties and potential future applications in biotechnology.

Polyether ionophores such as lysocellin are highly complex molecules, and many aspects of how they are formed in nature have remained unclear. In this study, the team identified an unusual enzyme, a cytochrome P450 called lyol, that performs a completely new type of chemical reaction. This step had never before been linked to the production of polyether ionophores and represents a fresh piece in the puzzle of how these compounds are made.

To reach their discovery, the researchers combined different approaches, including genome analysis, biochemical experiments, and in silico structural studies. Their results not only fill in a missing step in the biosynthetic pathway of lysocellin but also expand our understanding of how versatile P450 enzymes can be. Such enzymes are of great interest because they can carry out highly selective chemical transformations that are often difficult to achieve in the laboratory.

Looking ahead, this discovery opens the door to exploring other unusual P450 enzymes, also identified by the team, and their potential uses in biotechnology and synthetic biology. By harnessing nature’s own chemistry, researchers may develop new tools for producing valuable molecules in more sustainable ways.

This project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme.

Read the full open-access article here:
P450 Enzyme LyoI Performs Hydro-2,2′-Bifuran Oxidation in the Polyether Ionophore Lysocellin

Contact
Professor Thomas Poulsen
Aarhus Universitet
Department of Chemistry
Email: thpou@chem.au.dk