Biochemistry and Synthetic Metabolism
Our research is driven to discover and exploit new principles and mechanisms at the interface of microbial physiology, biochemistry and ecology. To that end we use a wide array of methods, including molecular biology and genetics, protein biochemistry, NMR, metabolomics, transcriptomics, proteomics, synthetic biology, and fluorescence microscopy. We are in intense exchange with other researchers worldwide, namely the laboratories and groups of Ivan Berg (University of Freiburg, D), John Gerlt (University of Illinois, US), Marc-Olivier Ebert (ETH Zurich, CH), Julia Vorholt (ETH Zurich, CH) and Arren Bar-Even (MPI for molecular Plant Physiology in Golm, D).
Dark metabolism: Discovering novel enzymes & pathways
Microbial metabolism controls the global cycling of elements, but how many novel pathways and enzymes are still undiscovered? Working in and collaborating with different international research groups, we were involved in the identification of several novel processes in the global carbon cycle that have been overlooked for a long time. Prominent examples are the ethylmalonyl-CoA pathway, the methylaspartate cycle, or the MTA-isoprenoid shunt. Our research has unraveled that Nature does not make use of a "uniformed biochemistry", as believed for a long time, but rather has invented many different biochemical solutions for one and the same purpose. Looking at the ever growing number of genes and proteins of "unknown functions" that derive from genome sequencing projects, we have apparently just begun to realize the evolutionary potential of Nature, and our search for novel reactions, enzymes, and pathways continues.
- Key publications:
- Könneke et al. PNAS 2014
- Erb et al. Nature Chem. Biol. 2012
- Khomyakova et al. Nature 2011
- Erb et al. PNAS 2007
Understanding and engineering enzyme catalysis
Enzymes are the essentials of metabolism, but how do they accelerate chemical reactions by several orders of magnitude? We have established analytical tools that allow us to resolve single steps of enzyme reactions to follow catalysis almost in "slow-motion". We use this technique to study important biochemical transformations. One of our central study objects is a novel class of CO2-fixing enzymes (reductive carboxylases) that belong to the most efficient CO2-fixing biocatalysts know so far. We are especially interested in identifying the molecular and evolutionary mechanisms that allow these proteins to bind CO2 and to promote carboxylation reactions so efficiently. How do these enzymes activate the thermodynamically and kinetically stable CO2 molecule? How did they emerge during evolution and can we use this information to design novel CO2-fixing enzymes?
- Key publications:
- Rosenthal et al. Nature Chem. Biol. 2017
- Peter et al. Angew. Chem. 2015
- Rosenthal et al. Nature Chem. Biol. 2015
Creating novel biology: synthetic pathways
Have we truly understood biology? Biological research remained primarily descriptive so far. However to convert it into a true scientific discipline, our most recent research approaches aim at constructing biological functionalities de novo. Inspired by Nature's creativity and using the methods of synthetic biology we aim at mimicking evolution by combining different enzymes into selected model organisms to construct and explore artificial pathways that have not been invented by nature (yet). From these efforts we hope to learn about the fundamental principles that form and shape metabolic pathways. At the same time we will provide novel biotechnological and sustainable solutions to human needs (e.g. for the production of value-added compounds from CO2).