Research projects in Kirschning Group
Synthetic chemistry is at home in a wide variety of ways in our research group. We use and combine synthetic chemistry, biotechnology and enabling technologies for drug-oriented natural product research. A sideline of these crossovers between synthetic chemistry and the biosciences concerns the question of the role of coenzymes and cofactors in the origin and evolution of life.
Natural product synthesis, structure elucidation and drug development
Our work on the total synthesis of natural products is embedded within a framework of a strategic partnership with the Helmholtz Center for Infection Research (Braunschweig/ Saarbrücken, Germany). We are working on the structural elucidation of new, biologically highly active secondary metabolites, their total and semi-synthesis and finally their biological and biomedical profile. Many of these natural products have either strong antiproliferative or antibacterial properties.
A telling example is Elansolid A, a polyketide macrolactone that exhibits antibacterial properties. We have been involved in the structure elucidation and developed a total synthesis which was designed in a biomimetic manner with respect to the central tetrahydroindane motif.
Expanding the terpenome using terpene cyclases
Terpenes are the largest and most diverse class of natural products. They are generated from a linear precursor - in the case of sesquiterpenes this is farnesyl pyrophosphate (FPP) - by means of a cationic cascade reaction. We study the promiscuity of sesquiterpene cyclases like presilphiperfolan-8-β-ol synthase (BcBot2) to expand the realm of terpenes and creating new annatural terpene backbones. This is exemplified for the heteroatom-modified tricyclic sesquiterpenoid. This chemoenzymatic strategy is complemented by the use of oxygenases and hydroxylases that selectively oxygenate the newly formed terpenoids which have the potential to expand the group of terpene-based fragrances and flavours.
Origin of life
The evolution of coenzymes and cofactors is fundamental for our own existence and yet, this topic is rarely discussed in contemporary science. Coenzymes are biological organocatalysts. Coenzymes are essential for functional biocatalysis in all living organisms and act as currency to regulate many basic metabolic processes. This theoretical and speculative topic which we supplement with a few experimental studies is intended to establish these small chemical entities as one (new) line in the chemical evolution. We regard them as key players in the transition from the abiotic to the biotic world.
