Our research is located at the interface of microbial physiology, biochemistry, and ecology, aiming to discover and engineer novel microbial pathways and enzymes that involve the transformation of carbon compounds, in particular acetate, methanol, methane or CO2. These compounds are central to the global carbon cycle, and their conversion through microbes has a direct impact on the concentration of greenhouse gases in the atmosphere.
We currently focus on answering the following questions: How many metabolic pathways in the global carbon cycle are still undiscovered and what is their ecological importance? How do enzymes catalyze challenging reactions (e.g. the fixation of CO2) and what drives their evolution? Can we construct novel enzymes and completely novel metabolic pathways (e.g., for the efficient fixation of CO2 into value-added compounds)? 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.
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.
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 known 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?
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).