News & Events
Prof. Thomas B. Brück, Ph.D.
Posted on November 15, 2019
Date - November 15, 2019
1:00 pm - 2:00 pm
Werner Siemens Chair of Synthetic Biotechnology and Director of the TUM AlgaeTec Center
Department of Chemistry, Technical University of Munich (TUM)
[Note: TUM just has been named German Excellence University for the third time in a row and is part of the Global Tech University alliance.]
Talk Title: Combinatorial Biocatalysis: A sustainable route for production of terpenoid bioactives
Macrocyclic sesqui (C15)- and diterpenes (C20) are a functionally diverse group of natural products with versatile bioactivities encompassing anti-cancer, anti-inflammatory and antimicrobial agents. However, the enormous structural complexity of these compounds often prevents economically efficient total synthesis. The recent developments in synthetic- and systems biology allow rapid identification of terpene centered biosynthesis pathways and identification of key biocatalytic modules from pro- and eukaryotic sources. The resulting information is the basis for sustainable terpene production routes using genetically engineered whole cell biocatalysts. The terpene synthase enzyme family is responsible for creating a diverse array of macrocyclic terpene olefins from the aliphatic substrates farnesyl- or geranylgeranyldiphosphate. Resulting structures such as amorphadiene and taxadien, form the backbone of the antimalarial compound artemisinin and the tumor therapeutic taxol respectively. In our combinatorial biocatalysis approach we combine molecular modelling with protein engineering methodologies to study terpene synthase mechanisms and diversify the respective enzyme product portfolio followed by enzyme mediated functionalization of the resulting macrocyclic scaffolds. The procedure provides for mass efficient, scalable production of natural and non-natural terpene type bioactives. This talk focuses on new biocatalytic production routes for the anti-inflammatory diterpene cyclooctatin and the bacterial synthase derived product isoelisabethatriene, a precursor en-route to the biosynthetic formation of pseudopterosins, a highly active class of marine coral derived anti-inflammatory and would healing compounds.