Elucidating the Biosynthesis of the Core Structure of Enediyne Natural Products

• Applicant: Dr. Lukas Lauterbach
• Subject Area: Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 509137346

The goal of the presented project ist the elucidation of the core-structure of the so-called enediyne natural products. This core consists of a cyclic polyketide with a 1,5-diyne-3-ene structural motif which is responsible for the antibiotic activity of these natural products. As the result of a Bergmann-cyclisation the core forms a benzoid-diradical that can cause DNA double-strand breaks. These compounds are therefore of special interest as potential anti-cancer therapeutics and some are already in clinical use as antibody-drug-conjugates to target specific malignant cell-lines. A deeper understanding towards the biosynthesis of this core-structure will facilitate the access to this group of natural products by enabling the biotechnological production of those compounds with the required enzymes. Additionally, further enzymes from the enediyne biosynthetic gene clusters will be investigated to address the diversity of the enediynes and generate a bigger source for potential future antibiotics. Apart from these mechanistic investigations, the characterisation of new gene clusters and their products will be an essential part of this project, This will be based on bioinformatic data generated from genome mining in newly sequenced genomes, previously extracted from bacteria out of the over 125,000 specimen spanning microbial strain collection of the Shen group.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Ben Shen, Ph.D.