biosynthesis of the Avionins, a new class of lantibiotics

• Applicant: Professor Dr. Roderich D. Süßmuth
• Subject Area: Biological and Biomimetic Chemistry
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 385052459

The ribosomally synthesised and posttranslationally modified peptide (RiPP) microvionine, isolated from a bacterium related to Actinomycetes, shows interesting antibacterial properties. In addition, it has a new combination of structural motifs, an avionine (avionylcysteine-labionine)-bridge and an N-terminal, bismethylated guanidino fatty acid. Due to its promising properties a deeper investigation of its biosynthesis of this forst lipolanthine (lipidated lanthipeptide) is planned. This should be achieved by modification and mutagenesis of the producing organism as well as by in vitro by protein-biochemical assays. Hence, not only the biosynthesis and the requirements for substrates are investigated, but also on an intermediate time scale derivatives of the drug with altered bioactivity are targeted to be produced. Furthermore, by genome mining more lipolanthine-producers will be identified and the corresponding compounds detected. Hence, a new group of lipidated RiPPs will be studies in-depth and the development of new antimicrobial drugs may be pushed forward.

• DFG Programme: Research Grants