Understanding and Building Metabolism

Our research is strongly team-oriented and highly interdisciplinary. Together we aim at transforming biology from an analytical-descriptive approach into a synthetic-constructive discipline that will allow us to find new solution for human needs (e.g., increased photosynthesis productivity or designer routes for the direct conversion of carbon dioxide into chemical and pharmaceutical building blocks or biofuels).

Dark metabolism: Discovering novel enzymes & pathways

Even though they are mostly invisible to our eyes, microorganisms are key players in the global carbon cycle and true masters of metabolism. But how many novel pathways and enzymes are still undiscovered? Collaborating with different international research groups, we were involved in the identification of several novel pathways 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 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 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 established analytical tools that allow us to resolve single steps of enzyme reactions to follow catalysis almost in "slow-motion".

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 a highly efficient carboxylation reactions. 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, Rosenthal et al. Nature Chem Biol 2015, Peter et al. Angew. Chem. 2015

Building artificial pathways and synthetic cells: Synthetic CO2-Fixation and Artificial Photosynthesis

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 functions de novo.

Using the methods of synthetic biology we aim at constructing and exploring completely artificial pathways that have not been invented by nature (yet). From these efforts we learn about the fundamental principles that form and shape metabolic pathways. At the same time we will provide novel, sustainable solutions for human needs (e.g., for the production of value-added compounds from CO2 or increased photosynthetic productivity).

Key publications: Schwander et al. Science 2016, Schada von Borzyskowski et al. ACS Synth. Biol. 2014

 

Compartmentalization and membrane functionalization

Many biochemical reactions require distinct chemical environments. With cells and organelles, nature found a very efficient way to provide ideal reaction spaces for biological processes. In addition to separating processes, biomembranes actively perform diverse fundamental biological processes, such as light harvesting and communication.
Our subgroup focuses on exploring the potentials of spatial separation and membrane biology to implement them in synthetic biology. We create artificial compartments and equip synthetic membranes with functional proteins to give them life-inspired properties. To achieve this goal, we work on:


• Biosynthesis of functional membrane proteins in synthetic membranes
• Functionalized nanopores for improved sensing and chemical/informational transport
• High-throughput production, analysis and selection of synthetic compartments to screen enzyme libraries for new-to-nature pathways
• Bottom-up energy regeneration modules for complex metabolic circuits


We apply state-of-the art methods, like microfluidics, cell-free protein synthesis, modern fluorescence microscopy methods, rational protein design and electrophysiological analysis of biomembranes.

 

At the “MGLN Team” of the Erb lab we bottom-up assemble Metabolic and Genetic Linked in vitro Networks, that we named MGLNs, where the programming of a genetically-encoded response into a metabolic network allows us to build advanced biomimetic systems with emergent properties such as decision-making, self-regeneration/repair, and evolution. For more details, click here

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