Felix Ecker

My PhD thesis explores the biochemical and structural details of enzymatic reactions in terpene biosynthesis. This vast class of natural products comprises close to 80,000 known substances that are essential players in the biological network of life, and manifest in almost all organisms. These compounds serve critical roles as hormones, vitamins, as well as defensive agents, and are indispensable for most cellular functions. The discovery of novel terpenes with potent antibacterial, antifungal, anti-inflammatory, or immunosuppressive properties could provide promising applications in medicine and agriculture.

Despite the incredible diversity amongst terpenes, their origins all trace back to isomeric C5 substrates, isopentenyl (IPP), and dimethylallyl pyrophosphate (DMAPP). Short chain isoprenyl diphosphate synthases (scIDS) catalyze the initial elongation to geranyl (GPP) and farnesyl pyrophosphate (FPP). In recent years, an scIDS in the leaf beetle Phaedon cochleariae (PcIDS1) was discovered to alter its product spectrum in response to bivalent metal ions like Mg²⁺ and Co²⁺. To understand this mechanism, extensive structural analyses were combined with thermal shift assays, substrate screening, as well as mutational studies. Through over 100,000 different crystallization conditions and parameters, dozens of molecular snapshots were obtained and pieced together, revealing a sophisticated communication network. The molecular system exploits slight differences in Lewis acidity of metal ions to regulate symmetry and dynamic interactions between the molecular reaction chambers. Such a multifunctional enzyme allows the insect to rapidly adapt to changes in environmental and nutritional conditions, producing either defensive monoterpenes from GPP or utilizing FPP for hormone synthesis.