Synthetic Cofactors and orthogonal Metabolism
Dr. Maren Nattermann
Research Area
In order to lower humanity’s dependency on fossil fuels, biocatalysis can be employed in the production of fine and bulk chemicals. Biocatalysts offer many advantages over traditional chemical synthesis, such as their ability to upcycle waste products like cellulose or carbon dioxide, or the very mild reaction conditions they enable (neutral pH, ambient temperature and pressure). In recent years, the number of biosynthetic pathways has been expanded beyond natural pathways, allowing the synthesis of new-to-nature chemicals via synthetic pathways.
However, the implementation of synthetic pathways into the living cell is challenging due to the delicate balance between growth and product generation. Any energy spent on off-pathway products or futile cycles can impede the implementation of a pathway: key cellular resources like ATP or NADPH may be drained or important metabolite pools such as acetyl-CoA disrupted, rendering the organism incapable of growth. In pathway engineering, a lot of effort is placed on minimizing these interactions, therefore allowing a better allocation of cellular resources. This is referred to as metabolic orthogonality.
Orthogonality can be achieved using non-natural intermediates that the surrounding metabolism does not recognize. However, pathways utilizing these synthetic intermediates still require key cellular resources in the form of cofactors (ATP, NADH, CoA, to name a few). In our group, we aim to expand the concept of orthogonality to those cofactor pools, creating separate cofactors for separate purposes.
